dataset_id
large_stringclasses
414 values
reaction_id
large_stringlengths
36
36
reaction_smiles
large_stringlengths
4
873
rxn_insight_reaction
large_stringlengths
19
1.07k
mapped_reaction_smiles
large_stringlengths
14
3.37k
reactant_smiles
large_stringlengths
1
581
product_smiles
large_stringlengths
1
433
reagent_smiles
large_stringclasses
634 values
catalyst_smiles
large_stringlengths
1
683
solvent_smiles
large_stringlengths
1
245
rxn_insight_class
large_stringclasses
11 values
rxn_insight_name
large_stringclasses
346 values
rxn_insight_tag
large_stringlengths
64
64
rxn_insight_tag2
large_stringlengths
64
64
rxn_insight_scaffold
large_stringlengths
5
288
rxn_insight_template
large_stringlengths
24
2.64k
yield_percent
float64
-0.8
90,205,160,000B
yield_measurements
large_stringlengths
2
864
temperature_value
float64
-230
30.1k
temperature_units
large_stringclasses
3 values
reaction_time_value
float64
0
4k
time_units
large_stringclasses
4 values
procedure_details
large_stringlengths
1
23.6k
reference
large_stringclasses
96 values
doi
large_stringclasses
19 values
functional_groups_reactants
large_stringlengths
3
716
functional_groups_products
large_stringlengths
3
539
participating_rings_reactants
large_stringlengths
5
293
participating_rings_products
large_stringlengths
5
271
all_rings_products
large_stringlengths
5
271
byproduct_smiles
large_stringclasses
176 values
agent_smiles
large_stringlengths
1
712
temperature_c
float64
-230
30.1k
reaction_time_hours
float64
0
2.16k
reaction_smiles_with_agents
large_stringlengths
4
882
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-7e290b33ebd64195870254e393a6bf70
CC(C)Oc1ccc(C(=O)O)cc1C#N.N[C@H](CCO)Cc1ccc(Br)cc1>>CC(C)Oc1ccc(C(=O)N[C@H](CCO)Cc2ccc(Br)cc2)cc1C#N
C(C)(C)N(C(C)C)CC.Cl.N[C@H](CCO)CC1=CC=C(C=C1)Br.C(#N)C=1C=C(C(=O)O)C=CC1OC(C)C.CN(C)C(=[N+](C)C)ON1C2=C(C=CC=C2)N=N1.F[P-](F)(F)(F)(F)F>>BrC1=CC=C(C=C1)C[C@@H](CCO)NC(C1=CC(=C(C=C1)OC(C)C)C#N)=O
O[C:9]([c:8]1[cH:7][cH:6][c:5]([O:4][CH:2]([CH3:1])[CH3:3])[c:25]([C:26]#[N:27])[cH:24]1)=[O:10].[NH2:11][C@H:12]([CH2:13][CH2:14][OH:15])[CH2:16][c:17]1[cH:18][cH:19][c:20]([Br:21])[cH:22][cH:23]1>>[CH3:1][CH:2]([CH3:3])[O:4][c:5]1[cH:6][cH:7][c:8]([C:9](=[O:10])[NH:11][C@H:12]([CH2:13][CH2:14][OH:15])[CH2:16][c:17]2[...
CC(C)Oc1ccc(C(=O)O)cc1C#N.N[C@H](CCO)Cc1ccc(Br)cc1
CC(C)Oc1ccc(C(=O)N[C@H](CCO)Cc2ccc(Br)cc2)cc1C#N
null
null
CN(C)C=O
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
O=C(NCCc1ccccc1)c1ccccc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C:6]-[C:7](-[C:8])-[NH2;D1;+0:9]>>[C:6]-[C:7](-[C:8])-[NH;D2;+0:9]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
78.7
[{"value": 78.0, "product": "BrC1=CC=C(C=C1)C[C@@H](CCO)NC(C1=CC(=C(C=C1)OC(C)C)C#N)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 78.7, "product": "BrC1=CC=C(C=C1)C[C@@H](CCO)NC(C1=CC(=C(C=C1)OC(C)C)C#N)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3
MINUTE
To a suspension of (3S)-3-Amino-4-(4-bromophenyl)-1-butanol hydrochloride (1.80 g, 6.42 mmol) in dry DMF (32 mL) was added N,N-diisopropylethyl amine (2.49 g, 19.3 mmol) and the resultant clear solution was stirred for 3 min. 3-Cyano-4-[(1-methylethyl)oxy]benzoic acid (1.45 g, 7.06 mmol) and HBTU (2.68 g, 7.06 mmol) we...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccccc1.c1ccccc1
HO-
CN(C)C=O
null
0.05
CC(C)Oc1ccc(C(=O)O)cc1C#N.N[C@H](CCO)Cc1ccc(Br)cc1>CN(C)C=O>CC(C)Oc1ccc(C(=O)N[C@H](CCO)Cc2ccc(Br)cc2)cc1C#N
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-5b4a8f3b0f7347b4a1f638591e81ba41
CC(C)Oc1ccc(C(=O)N[C@H](CCO)Cc2ccc(C(=O)CBr)cc2)cc1C#N.Cc1cccnc1N>>Cc1cccn2cc(-c3ccc(C[C@@H](CCO)NC(=O)c4ccc(OC(C)C)c(C#N)c4)cc3)nc12
C(=O)(O)[O-].[Na+].BrCC(=O)C1=CC=C(C=C1)C[C@@H](CCO)NC(C1=CC(=C(C=C1)OC(C)C)C#N)=O.NC1=NC=CC=C1C>>C(#N)C=1C=C(C(=O)N[C@H](CCO)CC2=CC=C(C=C2)C=2N=C3N(C=CC=C3C)C2)C=CC1OC(C)C
O=[C:8]([CH2:7]Br)[c:9]1[cH:10][cH:11][c:12]([CH2:13][C@@H:14]([CH2:15][CH2:16][OH:17])[NH:18][C:19](=[O:20])[c:21]2[cH:22][cH:23][c:24]([O:25][CH:26]([CH3:27])[CH3:28])[c:29]([C:30]#[N:31])[cH:32]2)[cH:33][cH:34]1.[CH3:1][c:2]1[cH:3][cH:4][cH:5][n:6][c:36]1[NH2:35]>>[CH3:1][c:2]1[cH:3][cH:4][cH:5][n:6]2[cH:7][c:8](-[c...
CC(C)Oc1ccc(C(=O)N[C@H](CCO)Cc2ccc(C(=O)CBr)cc2)cc1C#N.Cc1cccnc1N
Cc1cccn2cc(-c3ccc(C[C@@H](CCO)NC(=O)c4ccc(OC(C)C)c(C#N)c4)cc3)nc12
null
null
CC(C)O
Aromatic Heterocycle Formation
OtherReaction
98b9b4632b0457bc035e4a4d36e0a1658474c53cb0def2f4c4d097bbd0d48009
9e77d52183fdbe84f0d2ab96039aaf521caea9340e743bdc6436175f1a3bbdb6
O=C(NCCc1ccc(-c2cn3ccccc3n2)cc1)c1ccccc1
Br-[CH2;D2;+0:1]-[C;H0;D3;+0:2](=O)-[c;H0;D3;+0:3](:[c:4]:[c:5]):[c:6]:[c:7].[NH2;D1;+0:8]-[c:9](:[c:10]):[n;H0;D2;+0:11]:[c:12]:[c:13]>>[c:5]:[c:4]:[c;H0;D3;+0:3](-[c;H0;D3;+0:2]1:[cH;D2;+0:1]:[n;H0;D3;+0:11](:[c:12]:[c:13]):[c:9](:[c:10]):[n;H0;D2;+0:8]:1):[c:6]:[c:7]
70.3
[{"value": 70.0, "product": "C(#N)C=1C=C(C(=O)N[C@H](CCO)CC2=CC=C(C=C2)C=2N=C3N(C=CC=C3C)C2)C=CC1OC(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 70.3, "product": "C(#N)C=1C=C(C(=O)N[C@H](CCO)CC2=CC=C(C=C2)C=2N=C3N(C=CC=C3C)C2)C=CC1OC(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
7
HOUR
To a solution of N-((1S)-1-{[4-(bromoacetyl)phenyl]methyl}-3-hydroxypropyl)-3-cyano-4-[(1-methylethyl)oxy]benzamide (300 mg, 0.634 mmol) in i-PrOH (6 mL) was added 2-amino-3-picoline (Aldrich, 69 mg, 0.634 mmol) followed by solid NaHCO3 (64 mg, 0.761 mmol). The resultant suspension was heated to 80° C. After 7 h, a maj...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ketone.Primary amine
null
c1ccncc1
c1ccn2ccnc2c1
c1ccn2ccnc2c1.c1ccccc1.c1ccccc1
HBr
CC(C)O
null
7
CC(C)Oc1ccc(C(=O)N[C@H](CCO)Cc2ccc(C(=O)CBr)cc2)cc1C#N.Cc1cccnc1N>CC(C)O>Cc1cccn2cc(-c3ccc(C[C@@H](CCO)NC(=O)c4ccc(OC(C)C)c(C#N)c4)cc3)nc12
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-b0988497415649d58633ccc387509d59
Nc1ncccc1C=O>>CC(O)c1cccnc1N
NC1=NC=CC=C1C=O.C1CCOC1.[O-][Mn](=O)(=O)=O.[K+]>>NC1=NC=CC=C1C(C)O
[CH:2](=[O:3])[c:4]1[cH:5][cH:6][cH:7][n:8][c:9]1[NH2:10]>>[CH3:1][CH:2]([OH:3])[c:4]1[cH:5][cH:6][cH:7][n:8][c:9]1[NH2:10]
Nc1ncccc1C=O
CC(O)c1cccnc1N
null
null
null
Miscellaneous
OtherReaction
1ffaf80f172e20da969364a5d2977299bc51b204f2262675c45c8ec58ff36ac0
e005d650d08e61fc67b766830eb53235a9bc084cc3667d2f8a73c2fb8bb34277
c1ccncc1
[N;D1;H2:1]-[c:2](:[#7;a:3]:[c:4]):[c:5](-[CH;D2;+0:6]=[O;H0;D1;+0:7]):[c:8]>>[C;D1;H3:9]-[CH;D3;+0:6](-[OH;D1;+0:7])-[c:5](:[c:8]):[c:2](-[N;D1;H2:1]):[#7;a:3]:[c:4]
null
[]
null
null
null
null
To a dry flask (dried with a heat gun under argon purge) was added dry THF (400 mL) and MeLi-LiBr (137 mL of a 1.5 M solution in Et2O, 204.9 mmol) via cannula. This solution was cooled to −78° C. when a solution of 2-aminopyridine-3-carboxaldehyde (10.0 g, 82.0 mmol) in THF (150 mL) was added dropwise via a pressure eq...
10.6084/m9.figshare.5104873.v1
null
Aldehyde
Secondary alcohol
null
null
c1ccncc1
Other
null
null
null
Nc1ncccc1C=O>>CC(O)c1cccnc1N
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-fc631dfab8ca41659de32fe1acc8901c
CC(C)Oc1ccc(C(=O)Oc2c(F)c(F)c(F)c(F)c2F)cc1Cl.CC(O)c1cccn2cc(-c3ccc(C[C@@H](CCO)N(C(=O)[O-])C(C)(C)C)cc3)nc12>>CC(C)Oc1ccc(C(=O)N[C@H](CCO)Cc2ccc(-c3cn4cccc(C(C)O)c4n3)cc2)cc1Cl
CC(C)(C)N(C([O-])=O)[C@H](CCO)CC1=CC=C(C=C1)C=1N=C2N(C=CC=C2C(C)O)C1.Cl.O1CCOCC1.C(C)(C)N(C(C)C)CC.ClC=1C=C(C(=O)OC2=C(C(=C(C(=C2F)F)F)F)F)C=CC1OC(C)C>>ClC=1C=C(C(=O)N[C@H](CCO)CC2=CC=C(C=C2)C=2N=C3N(C=CC=C3C(C)O)C2)C=CC1OC(C)C
Fc1c(F)c(F)c(O[C:9]([c:8]2[cH:7][cH:6][c:5]([O:4][CH:2]([CH3:1])[CH3:3])[c:36]([Cl:37])[cH:35]2)=[O:10])c(F)c1F.CC(C)(C)[N:11](C(=O)[O-])[C@H:12]([CH2:13][CH2:14][OH:15])[CH2:16][c:17]1[cH:18][cH:19][c:20](-[c:21]2[cH:22][n:23]3[cH:24][cH:25][cH:26][c:27]([CH:28]([CH3:29])[OH:30])[c:31]3[n:32]2)[cH:33][cH:34]1>>[CH3:1]...
CC(C)Oc1ccc(C(=O)Oc2c(F)c(F)c(F)c(F)c2F)cc1Cl.CC(O)c1cccn2cc(-c3ccc(C[C@@H](CCO)N(C(=O)[O-])C(C)(C)C)cc3)nc12
CC(C)Oc1ccc(C(=O)N[C@H](CCO)Cc2ccc(-c3cn4cccc(C(C)O)c4n3)cc2)cc1Cl
null
null
O
Acylation
OtherReaction
99c7e5ccb14cd05d201fc9d814902a93f26d22f6be437b04170d6760e6ca8897
42472522721b7f81fc665a4fc38a467af73eaadcae06dde15cdffe1a6c2c71eb
O=C(NCCc1ccc(-c2cn3ccccc3n2)cc1)c1ccccc1
C-C(-C)(-C)-[N;H0;D3;+0:1](-C(=O)-[O-])-[C:2](-[C:3])-[C:4].F-c1:c(-F):c(-F):c(-O-[C;H0;D3;+0:5](=[O;D1;H0:6])-[c:7](:[c:8]):[c:9]):c(-F):c:1-F>>[C:3]-[C:2](-[C:4])-[NH;D2;+0:1]-[C;H0;D3;+0:5](=[O;D1;H0:6])-[c:7](:[c:8]):[c:9]
53
[{"value": 53.0, "product": "ClC=1C=C(C(=O)N[C@H](CCO)CC2=CC=C(C=C2)C=2N=C3N(C=CC=C3C(C)O)C2)C=CC1OC(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 52.8, "product": "ClC=1C=C(C(=O)N[C@H](CCO)CC2=CC=C(C=C2)C=2N=C3N(C=CC=C3C(C)O)C2)C=CC1OC(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
30
MINUTE
A mixture of 1,1-dimethylethyl[(1S)-3-hydroxy-1-({4-[8-(1-hydroxyethyl)imidazo[1,2-a]pyridin-2-yl]phenyl}methyl)propyl]carbamate (1.08 g, 2.54 mmol) and 4M HCl in 1,4-dioxane (8.0 mL, 32 mmol) was stirred at room temperature for 30 minutes. The reaction was concentrated to dryness redissolved in DMF (25 mL), and to thi...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic halide.Aromatic halide.Aromatic halide.Aromatic halide.Carbamic acid.Ester
Secondary amide
c1ccccc1
null
c1ccccc1.c1ccccc1.c1ccn2ccnc2c1
HF
O
null
0.5
CC(C)Oc1ccc(C(=O)Oc2c(F)c(F)c(F)c(F)c2F)cc1Cl.CC(O)c1cccn2cc(-c3ccc(C[C@@H](CCO)N(C(=O)[O-])C(C)(C)C)cc3)nc12>O>CC(C)Oc1ccc(C(=O)N[C@H](CCO)Cc2ccc(-c3cn4cccc(C(C)O)c4n3)cc2)cc1Cl
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-478a448d2e5e45c7bb3668396804fe41
CC(C)Oc1ccc(C(=O)Oc2c(F)c(F)c(F)c(F)c2F)cc1Cl.CC(O)c1cccn2cc(-c3ccc(C[C@@H](CN4C(=O)c5ccccc5C4=O)N(C(=O)[O-])C(C)(C)C)cc3)nc12>>CC(C)Oc1ccc(C(=O)N[C@@H](Cc2ccc(-c3cn4cccc(C(C)O)c4n3)cc2)CN2C(=O)c3ccccc3C2=O)cc1Cl
CC(C)(C)N(C([O-])=O)[C@H](CN1C(C2=CC=CC=C2C1=O)=O)CC1=CC=C(C=C1)C=1N=C2N(C=CC=C2C(C)O)C1.Cl.O1CCOCC1.C(C)(C)N(C(C)C)CC.ClC=1C=C(C(=O)OC2=C(C(=C(C(=C2F)F)F)F)F)C=CC1OC(C)C>>ClC=1C=C(C(=O)N[C@H](CN2C(C3=CC=CC=C3C2=O)=O)CC2=CC=C(C=C2)C=2N=C3N(C=CC=C3C(C)O)C2)C=CC1OC(C)C
Fc1c(F)c(F)c(O[C:9]([c:8]2[cH:7][cH:6][c:5]([O:4][CH:2]([CH3:1])[CH3:3])[c:45]([Cl:46])[cH:44]2)=[O:10])c(F)c1F.CC(C)(C)[N:11](C(=O)[O-])[C@@H:12]([CH2:13][c:14]1[cH:15][cH:16][c:17](-[c:18]2[cH:19][n:20]3[cH:21][cH:22][cH:23][c:24]([CH:25]([CH3:26])[OH:27])[c:28]3[n:29]2)[cH:30][cH:31]1)[CH2:32][N:33]1[C:34](=[O:35])[...
CC(C)Oc1ccc(C(=O)Oc2c(F)c(F)c(F)c(F)c2F)cc1Cl.CC(O)c1cccn2cc(-c3ccc(C[C@@H](CN4C(=O)c5ccccc5C4=O)N(C(=O)[O-])C(C)(C)C)cc3)nc12
CC(C)Oc1ccc(C(=O)N[C@@H](Cc2ccc(-c3cn4cccc(C(C)O)c4n3)cc2)CN2C(=O)c3ccccc3C2=O)cc1Cl
null
null
O
Acylation
OtherReaction
99c7e5ccb14cd05d201fc9d814902a93f26d22f6be437b04170d6760e6ca8897
42472522721b7f81fc665a4fc38a467af73eaadcae06dde15cdffe1a6c2c71eb
O=C(N[C@@H](Cc1ccc(-c2cn3ccccc3n2)cc1)CN1C(=O)c2ccccc2C1=O)c1ccccc1
C-C(-C)(-C)-[N;H0;D3;+0:1](-C(=O)-[O-])-[C:2](-[C:3])-[C:4].F-c1:c(-F):c(-F):c(-O-[C;H0;D3;+0:5](=[O;D1;H0:6])-[c:7](:[c:8]):[c:9]):c(-F):c:1-F>>[C:3]-[C:2](-[C:4])-[NH;D2;+0:1]-[C;H0;D3;+0:5](=[O;D1;H0:6])-[c:7](:[c:8]):[c:9]
100
[{"value": 100.0, "product": "ClC=1C=C(C(=O)N[C@H](CN2C(C3=CC=CC=C3C2=O)=O)CC2=CC=C(C=C2)C=2N=C3N(C=CC=C3C(C)O)C2)C=CC1OC(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 99.6, "product": "ClC=1C=C(C(=O)N[C@H](CN2C(C3=CC=CC=C3C2=O)=O)CC2=CC=C(C=C2)C=2N=C3N(C=CC=C3C(C)O)C2)C=CC1OC(C)C", "details": "CALCU...
null
null
45
MINUTE
A mixture of 1,1-dimethylethyl[(1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-({4-[8-(1-hydroxyethyl)imidazo[1,2-a]pyridin-2-yl]phenyl}methyl)ethyl]carbamate (1.79 g, 3.31 mmol) and 4 M HCl in 1,4-dioxane (20 mL, 80 mmol) was stirred at room temperature for 45 minutes. The reaction was concentrated to dryness and re...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic halide.Aromatic halide.Aromatic halide.Aromatic halide.Carbamic acid.Ester
Secondary amide
c1ccccc1
null
c1ccccc1.c1ccccc1.c1ccn2ccnc2c1.c1ccc2c(c1)C[NH]C2
HF
O
null
0.75
CC(C)Oc1ccc(C(=O)Oc2c(F)c(F)c(F)c(F)c2F)cc1Cl.CC(O)c1cccn2cc(-c3ccc(C[C@@H](CN4C(=O)c5ccccc5C4=O)N(C(=O)[O-])C(C)(C)C)cc3)nc12>O>CC(C)Oc1ccc(C(=O)N[C@@H](Cc2ccc(-c3cn4cccc(C(C)O)c4n3)cc2)CN2C(=O)c3ccccc3C2=O)cc1Cl
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-13830506cd3842dfbbdbd14368e7f92f
CC(C)Oc1ccc(C(=O)N[C@@H](Cc2ccc(-c3cn4cccc(C(C)O)c4n3)cc2)CN2C(=O)c3ccccc3C2=O)cc1Cl>>CC(C)Oc1ccc(C(=O)N[C@H](CN)Cc2ccc(-c3cn4cccc(C(C)O)c4n3)cc2)cc1Cl
ClC=1C=C(C(=O)N[C@H](CN2C(C3=CC=CC=C3C2=O)=O)CC2=CC=C(C=C2)C=2N=C3N(C=CC=C3C(C)O)C2)C=CC1OC(C)C.O.NN>>NC[C@H](CC1=CC=C(C=C1)C=1N=C2N(C=CC=C2C(C)O)C1)NC(C1=CC(=C(C=C1)OC(C)C)Cl)=O
O=C1c2ccccc2C(=O)[N:14]1[CH2:13][C@@H:12]([NH:11][C:9]([c:8]1[cH:7][cH:6][c:5]([O:4][CH:2]([CH3:1])[CH3:3])[c:35]([Cl:36])[cH:34]1)=[O:10])[CH2:15][c:16]1[cH:17][cH:18][c:19](-[c:20]2[cH:21][n:22]3[cH:23][cH:24][cH:25][c:26]([CH:27]([CH3:28])[OH:29])[c:30]3[n:31]2)[cH:32][cH:33]1>>[CH3:1][CH:2]([CH3:3])[O:4][c:5]1[cH:6...
CC(C)Oc1ccc(C(=O)N[C@@H](Cc2ccc(-c3cn4cccc(C(C)O)c4n3)cc2)CN2C(=O)c3ccccc3C2=O)cc1Cl
CC(C)Oc1ccc(C(=O)N[C@H](CN)Cc2ccc(-c3cn4cccc(C(C)O)c4n3)cc2)cc1Cl
null
null
C(C)O
Reduction
Phthalimide deprotection
d9f63cee80ef758bd939ff2a10772447b3092f1576180488281833a98eb1691a
dbfe4201a9328005dfaec4c3f363ddbb4ef3c9b825f648735dc97b2b57396333
O=C(NCCc1ccc(-c2cn3ccccc3n2)cc1)c1ccccc1
O=C1-[N;H0;D3;+0:1](-[C:2]-[C:3])-C(=O)-c2:c:c:c:c:c:2-1>>[C:3]-[C:2]-[NH2;D1;+0:1]
100
[{"value": 100.0, "product": "NC[C@H](CC1=CC=C(C=C1)C=1N=C2N(C=CC=C2C(C)O)C1)NC(C1=CC(=C(C=C1)OC(C)C)Cl)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 99.8, "product": "NC[C@H](CC1=CC=C(C=C1)C=1N=C2N(C=CC=C2C(C)O)C1)NC(C1=CC(=C(C=C1)OC(C)C)Cl)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": fals...
57
CELSIUS
null
null
A mixture of 3-chloro-N-[(1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-({4-[8-(1-hydroxyethyl)imidazo[1,2-a]pyridin-2-yl]phenyl}methyl)ethyl]-4-[(1-methylethyl)oxy]benzamide (2.10 g, 3.30 mmol) and hydrazine monohydrate (0.83 g, 16.5 mmol) in ethanol (30 mL) was heated at 57° C. overnight. The reaction was cooled, ...
10.6084/m9.figshare.5104873.v1
null
Substituted dicarboximide
Primary amine
c1ccc2c(c1)C[NH]C2
null
c1ccccc1.c1ccccc1.c1ccn2ccnc2c1
HO-
C(C)O
57
null
CC(C)Oc1ccc(C(=O)N[C@@H](Cc2ccc(-c3cn4cccc(C(C)O)c4n3)cc2)CN2C(=O)c3ccccc3C2=O)cc1Cl>C(C)O>CC(C)Oc1ccc(C(=O)N[C@H](CN)Cc2ccc(-c3cn4cccc(C(C)O)c4n3)cc2)cc1Cl
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-b356287b5efa4f85b4f2763401f046a9
CC(C)Oc1ccc(C(=O)N[C@H](CN)Cc2ccc(-c3cn4cccc(C(C)O)c4n3)cc2)cc1Cl.CN(C)CC(=O)O>>CC(C)Oc1ccc(C(=O)N[C@H](CNC(=O)CN(C)C)Cc2ccc(-c3cn4cccc(C(C)O)c4n3)cc2)cc1Cl
NC[C@H](CC1=CC=C(C=C1)C=1N=C2N(C=CC=C2C(C)O)C1)NC(C1=CC(=C(C=C1)OC(C)C)Cl)=O.CCN=C=NCCCN(C)C.C(C)(C)N(C(C)C)CC.CN(CC(=O)O)C>>ClC=1C=C(C(=O)N[C@H](CNC(CN(C)C)=O)CC2=CC=C(C=C2)C=2N=C3N(C=CC=C3C(C)O)C2)C=CC1OC(C)C
[CH3:1][CH:2]([CH3:3])[O:4][c:5]1[cH:6][cH:7][c:8]([C:9](=[O:10])[NH:11][C@H:12]([CH2:13][NH2:14])[CH2:21][c:22]2[cH:23][cH:24][c:25](-[c:26]3[cH:27][n:28]4[cH:29][cH:30][cH:31][c:32]([CH:33]([CH3:34])[OH:35])[c:36]4[n:37]3)[cH:38][cH:39]2)[cH:40][c:41]1[Cl:42].O[C:15](=[O:16])[CH2:17][N:18]([CH3:19])[CH3:20]>>[CH3:1][...
CC(C)Oc1ccc(C(=O)N[C@H](CN)Cc2ccc(-c3cn4cccc(C(C)O)c4n3)cc2)cc1Cl.CN(C)CC(=O)O
CC(C)Oc1ccc(C(=O)N[C@H](CNC(=O)CN(C)C)Cc2ccc(-c3cn4cccc(C(C)O)c4n3)cc2)cc1Cl
null
null
O.C(Cl)Cl
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
O=C(NCCc1ccc(-c2cn3ccccc3n2)cc1)c1ccccc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[#7:4].[C:5]-[C:6]-[NH2;D1;+0:7]>>[#7:4]-[C:3]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:7]-[C:6]-[C:5]
48.3
[{"value": 48.0, "product": "ClC=1C=C(C(=O)N[C@H](CNC(CN(C)C)=O)CC2=CC=C(C=C2)C=2N=C3N(C=CC=C3C(C)O)C2)C=CC1OC(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 48.3, "product": "ClC=1C=C(C(=O)N[C@H](CNC(CN(C)C)=O)CC2=CC=C(C=C2)C=2N=C3N(C=CC=C3C(C)O)C2)C=CC1OC(C)C", "details": "CALCULATEDPERCENTYIELD", "...
null
null
8
HOUR
A mixture of N-[(1S)-2-amino-1-({4-[8-(1-hydroxyethyl)imidazo[1,2-a]pyridin-2-yl]phenyl}methyl)ethyl]-3-chloro-4-[(1-methylethyl)oxy]benzamide (0.912 g, 1.80 mmol), EDCI (0.69 g, 3.6 mmol), N,N-diisopropylethylamine (0.466 g, 3.6 mmol), and N,N-dimethylglycine (0.372 g, 3.6 mmol) in methylene chloride (17 mL) was stirr...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccccc1.c1ccccc1.c1ccn2ccnc2c1
HO-
O.C(Cl)Cl
null
8
CC(C)Oc1ccc(C(=O)N[C@H](CN)Cc2ccc(-c3cn4cccc(C(C)O)c4n3)cc2)cc1Cl.CN(C)CC(=O)O>O.C(Cl)Cl>CC(C)Oc1ccc(C(=O)N[C@H](CNC(=O)CN(C)C)Cc2ccc(-c3cn4cccc(C(C)O)c4n3)cc2)cc1Cl
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-e45590cc49e643b99b114b7b14e81c1d
CC(C)(C)N(C(=O)[O-])[C@@H](Cc1ccc(-c2cn3cccc(Br)c3n2)cc1)CN1C(=O)c2ccccc2C1=O.CC(C)Oc1ccc(C(=O)Oc2c(F)c(F)c(F)c(F)c2F)cc1Cl>>CC(C)Oc1ccc(C(=O)N[C@@H](Cc2ccc(-c3cn4cccc(Br)c4n3)cc2)CN2C(=O)c3ccccc3C2=O)cc1Cl
C(C)(C)N(CC)C(C)C.CC(C)(C)N(C([O-])=O)[C@@H](CC1=CC=C(C=C1)C=1N=C2N(C=CC=C2Br)C1)CN1C(C2=CC=CC=C2C1=O)=O.Cl.ClC=1C=C(C(=O)OC2=C(C(=C(C(=C2F)F)F)F)F)C=CC1OC(C)C>>BrC=1C=2N(C=CC1)C=C(N2)C2=CC=C(C=C2)C[C@@H](CN2C(C1=CC=CC=C1C2=O)=O)NC(C2=CC(=C(C=C2)OC(C)C)Cl)=O
CC(C)(C)[N:11](C(=O)[O-])[C@@H:12]([CH2:13][c:14]1[cH:15][cH:16][c:17](-[c:18]2[cH:19][n:20]3[cH:21][cH:22][cH:23][c:24]([Br:25])[c:26]3[n:27]2)[cH:28][cH:29]1)[CH2:30][N:31]1[C:32](=[O:33])[c:34]2[cH:35][cH:36][cH:37][cH:38][c:39]2[C:40]1=[O:41].Fc1c(F)c(F)c(O[C:9]([c:8]2[cH:7][cH:6][c:5]([O:4][CH:2]([CH3:1])[CH3:3])[...
CC(C)(C)N(C(=O)[O-])[C@@H](Cc1ccc(-c2cn3cccc(Br)c3n2)cc1)CN1C(=O)c2ccccc2C1=O.CC(C)Oc1ccc(C(=O)Oc2c(F)c(F)c(F)c(F)c2F)cc1Cl
CC(C)Oc1ccc(C(=O)N[C@@H](Cc2ccc(-c3cn4cccc(Br)c4n3)cc2)CN2C(=O)c3ccccc3C2=O)cc1Cl
null
null
O1CCOCC1.C(C)(=O)OCC
Acylation
OtherReaction
99c7e5ccb14cd05d201fc9d814902a93f26d22f6be437b04170d6760e6ca8897
42472522721b7f81fc665a4fc38a467af73eaadcae06dde15cdffe1a6c2c71eb
O=C(N[C@@H](Cc1ccc(-c2cn3ccccc3n2)cc1)CN1C(=O)c2ccccc2C1=O)c1ccccc1
C-C(-C)(-C)-[N;H0;D3;+0:1](-C(=O)-[O-])-[C:2](-[C:3])-[C:4].F-c1:c(-F):c(-F):c(-O-[C;H0;D3;+0:5](=[O;D1;H0:6])-[c:7](:[c:8]):[c:9]):c(-F):c:1-F>>[C:3]-[C:2](-[C:4])-[NH;D2;+0:1]-[C;H0;D3;+0:5](=[O;D1;H0:6])-[c:7](:[c:8]):[c:9]
65
[{"value": 65.0, "product": null, "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 1,1-dimethylethyl{(1S)-2-[4-(8-bromoimidazo[1,2-a]pyridin-2-yl)phenyl]-1-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2yl)methyl]ethyl)carbamate (3.5 mmol) and hydrogen chloride in 1,4-dioxane (20 mL, 4.0 M) was stirred for 1 h at RT. The reaction was concentrated to dryness and redissolved in N,N-dimethylformamid...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic halide.Aromatic halide.Aromatic halide.Aromatic halide.Carbamic acid.Ester
Secondary amide
c1ccccc1
null
c1ccccc1.c1ccccc1.c1ccn2ccnc2c1.c1ccc2c(c1)C[NH]C2
HF
O1CCOCC1.C(C)(=O)OCC
null
null
CC(C)(C)N(C(=O)[O-])[C@@H](Cc1ccc(-c2cn3cccc(Br)c3n2)cc1)CN1C(=O)c2ccccc2C1=O.CC(C)Oc1ccc(C(=O)Oc2c(F)c(F)c(F)c(F)c2F)cc1Cl>O1CCOCC1.C(C)(=O)OCC>CC(C)Oc1ccc(C(=O)N[C@@H](Cc2ccc(-c3cn4cccc(Br)c4n3)cc2)CN2C(=O)c3ccccc3C2=O)cc1Cl
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ae0b6e6c8e8a4274b8119ea5763f3b0d
CC(C)Oc1ccc(C(=O)N[C@@H](Cc2ccc(-c3cn4cccc(Br)c4n3)cc2)CN2C(=O)c3ccccc3C2=O)cc1Cl>>CC(C)Oc1ccc(C(=O)N[C@H](CN)Cc2ccc(-c3cn4cccc(Br)c4n3)cc2)cc1Cl
BrC=1C=2N(C=CC1)C=C(N2)C2=CC=C(C=C2)C[C@@H](CN2C(C1=CC=CC=C1C2=O)=O)NC(C2=CC(=C(C=C2)OC(C)C)Cl)=O.O.NN>>NC[C@H](CC1=CC=C(C=C1)C=1N=C2N(C=CC=C2Br)C1)NC(C1=CC(=C(C=C1)OC(C)C)Cl)=O
O=C1c2ccccc2C(=O)[N:14]1[CH2:13][C@@H:12]([NH:11][C:9]([c:8]1[cH:7][cH:6][c:5]([O:4][CH:2]([CH3:1])[CH3:3])[c:33]([Cl:34])[cH:32]1)=[O:10])[CH2:15][c:16]1[cH:17][cH:18][c:19](-[c:20]2[cH:21][n:22]3[cH:23][cH:24][cH:25][c:26]([Br:27])[c:28]3[n:29]2)[cH:30][cH:31]1>>[CH3:1][CH:2]([CH3:3])[O:4][c:5]1[cH:6][cH:7][c:8]([C:9...
CC(C)Oc1ccc(C(=O)N[C@@H](Cc2ccc(-c3cn4cccc(Br)c4n3)cc2)CN2C(=O)c3ccccc3C2=O)cc1Cl
CC(C)Oc1ccc(C(=O)N[C@H](CN)Cc2ccc(-c3cn4cccc(Br)c4n3)cc2)cc1Cl
null
null
C(C)O
Reduction
Phthalimide deprotection
d9f63cee80ef758bd939ff2a10772447b3092f1576180488281833a98eb1691a
dbfe4201a9328005dfaec4c3f363ddbb4ef3c9b825f648735dc97b2b57396333
O=C(NCCc1ccc(-c2cn3ccccc3n2)cc1)c1ccccc1
O=C1-[N;H0;D3;+0:1](-[C:2]-[C:3])-C(=O)-c2:c:c:c:c:c:2-1>>[C:3]-[C:2]-[NH2;D1;+0:1]
null
[]
50
CELSIUS
18
HOUR
To a solution of N-{(1S)-2-[4-(8-bromoimidazo[1,2-a]pyridin-2-yl)phenyl]-1-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]ethyl)-3-chloro-4-[(1-methylethyl)oxy]benzamide (1.5 mmol) in ethanol (10 mL) was added hydrazine monohydrate (7.6 mmol). The reaction stirred for 18 h at 50° C. upon which a white precipitate form...
10.6084/m9.figshare.5104873.v1
null
Substituted dicarboximide
Primary amine
c1ccc2c(c1)C[NH]C2
null
c1ccccc1.c1ccccc1.c1ccn2ccnc2c1
HO-
C(C)O
50
18
CC(C)Oc1ccc(C(=O)N[C@@H](Cc2ccc(-c3cn4cccc(Br)c4n3)cc2)CN2C(=O)c3ccccc3C2=O)cc1Cl>C(C)O>CC(C)Oc1ccc(C(=O)N[C@H](CN)Cc2ccc(-c3cn4cccc(Br)c4n3)cc2)cc1Cl
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-9a7192fcea0e4e09a803dec294fa9dfd
CC(C)Oc1ccc(C(=O)N[C@H](CN)Cc2ccc(-c3cn4cccc(Br)c4n3)cc2)cc1Cl.C[C@@H](NC(=O)OC(C)(C)C)C(=O)O>>CC(C)Oc1ccc(C(=O)N[C@H](CNC(=O)[C@@H](C)N)Cc2ccc(-c3cn4cccc(Br)c4n3)cc2)cc1Cl
NC[C@H](CC1=CC=C(C=C1)C=1N=C2N(C=CC=C2Br)C1)NC(C1=CC(=C(C=C1)OC(C)C)Cl)=O.CC(C)(C)OC(=O)N[C@H](C)C(=O)O.CCN=C=NCCCN(C)C.Cl>>N[C@H](C)C(=O)NC[C@H](CC1=CC=C(C=C1)C=1N=C2N(C=CC=C2Br)C1)NC(C1=CC(=C(C=C1)OC(C)C)Cl)=O
[CH3:1][CH:2]([CH3:3])[O:4][c:5]1[cH:6][cH:7][c:8]([C:9](=[O:10])[NH:11][C@H:12]([CH2:13][NH2:14])[CH2:20][c:21]2[cH:22][cH:23][c:24](-[c:25]3[cH:26][n:27]4[cH:28][cH:29][cH:30][c:31]([Br:32])[c:33]4[n:34]3)[cH:35][cH:36]2)[cH:37][c:38]1[Cl:39].CC(C)(C)OC(=O)[NH:19][C@@H:17]([C:15](O)=[O:16])[CH3:18]>>[CH3:1][CH:2]([CH...
CC(C)Oc1ccc(C(=O)N[C@H](CN)Cc2ccc(-c3cn4cccc(Br)c4n3)cc2)cc1Cl.C[C@@H](NC(=O)OC(C)(C)C)C(=O)O
CC(C)Oc1ccc(C(=O)N[C@H](CNC(=O)[C@@H](C)N)Cc2ccc(-c3cn4cccc(Br)c4n3)cc2)cc1Cl
null
null
O1CCOCC1.C(Cl)Cl
Acylation
OtherReaction
b4c20342f55b434660078663f02be082076e2ff9b9068db91acc0b381022a32e
e525bb030a9f5f4a2fc47bce923bf921a3769ce3300b3fa2600575194671a3f3
O=C(NCCc1ccc(-c2cn3ccccc3n2)cc1)c1ccccc1
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[C:2](-[C;D1;H3:3])-[C;H0;D3;+0:4](-O)=[O;D1;H0:5].[C:6]-[C:7]-[NH2;D1;+0:8]>>[C:6]-[C:7]-[NH;D2;+0:8]-[C;H0;D3;+0:4](=[O;D1;H0:5])-[C:2](-[C;D1;H3:3])-[NH2;D1;+0:1]
25
[{"value": 25.0, "product": "N[C@H](C)C(=O)NC[C@H](CC1=CC=C(C=C1)C=1N=C2N(C=CC=C2Br)C1)NC(C1=CC(=C(C=C1)OC(C)C)Cl)=O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
A solution of N-((1S)-2-amino-1-{[4-(8-bromoimidazo[1,2-a]pyridin-2-yl)phenyl]methyl}ethyl)-3-chloro-4-[(1-methylethyl)oxy]benzamide (0.28 mmol), N-{[(1,1-dimethylethyl)oxy]carbonyl}-D-alanine (0.56 mmol), EDCI (0.56 mmol), and TEA (1.12 mmol) stirred in methylene chloride (2 mL) at RT for 18 h. The reaction was then t...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Carboxylic acid.Ether.Primary amine.Boc
Secondary amide.Primary amine
null
null
c1ccccc1.c1ccccc1.c1ccn2ccnc2c1
HO-
O1CCOCC1.C(Cl)Cl
null
1
CC(C)Oc1ccc(C(=O)N[C@H](CN)Cc2ccc(-c3cn4cccc(Br)c4n3)cc2)cc1Cl.C[C@@H](NC(=O)OC(C)(C)C)C(=O)O>O1CCOCC1.C(Cl)Cl>CC(C)Oc1ccc(C(=O)N[C@H](CNC(=O)[C@@H](C)N)Cc2ccc(-c3cn4cccc(Br)c4n3)cc2)cc1Cl
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-1b38ea44be01460e8865c06d3f979b70
CC(C)(N)C(=O)O.Cc1cccn2cc(-c3ccc(C[C@@H](CN)NC(=O)c4ccc(OC(C)C)c(Cl)c4)cc3)nc12>>Cc1cccn2cc(-c3ccc(C[C@@H](CNC(=O)C(C)(C)N)NC(=O)c4ccc(OC(C)C)c(Cl)c4)cc3)nc12
NC[C@H](CC1=CC=C(C=C1)C=1N=C2N(C=CC=C2C)C1)NC(C1=CC(=C(C=C1)OC(C)C)Cl)=O.CC(N)(C)C(=O)O>>ClC=1C=C(C(=O)N[C@H](CNC(C(N)(C)C)=O)CC2=CC=C(C=C2)C=2N=C3N(C=CC=C3C)C2)C=CC1OC(C)C
O[C:17](=[O:18])[C:19]([CH3:20])([CH3:21])[NH2:22].[CH3:1][c:2]1[cH:3][cH:4][cH:5][n:6]2[cH:7][c:8](-[c:9]3[cH:10][cH:11][c:12]([CH2:13][C@@H:14]([CH2:15][NH2:16])[NH:23][C:24](=[O:25])[c:26]4[cH:27][cH:28][c:29]([O:30][CH:31]([CH3:32])[CH3:33])[c:34]([Cl:35])[cH:36]4)[cH:37][cH:38]3)[n:39][c:40]12>>[CH3:1][c:2]1[cH:3]...
CC(C)(N)C(=O)O.Cc1cccn2cc(-c3ccc(C[C@@H](CN)NC(=O)c4ccc(OC(C)C)c(Cl)c4)cc3)nc12
Cc1cccn2cc(-c3ccc(C[C@@H](CNC(=O)C(C)(C)N)NC(=O)c4ccc(OC(C)C)c(Cl)c4)cc3)nc12
null
null
null
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
O=C(NCCc1ccc(-c2cn3ccccc3n2)cc1)c1ccccc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C;D1;H3:4])(-[C;D1;H3:5])-[N;D1;H2:6].[C:7]-[C:8]-[NH2;D1;+0:9]>>[C:7]-[C:8]-[NH;D2;+0:9]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C;D1;H3:4])(-[C;D1;H3:5])-[N;D1;H2:6]
null
[]
null
null
null
null
Following the procedure described above with N-((1S)-2-amino-1-{[4-(8-methylimidazo[1,2-a]pyridin-2-yl)phenyl]methyl}ethyl)-3-chloro-4-[(1-methylethyl)oxy]benzamide and N-[(1,1-dimethylethyl)oxy]carbonyl)-2-methylalanine provided the title product as a white solid. ESMS [M+H]+: 563.2. Conditions: See reaction.notes.pro...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccn2ccnc2c1.c1ccccc1.c1ccccc1
HO-
null
null
null
CC(C)(N)C(=O)O.Cc1cccn2cc(-c3ccc(C[C@@H](CN)NC(=O)c4ccc(OC(C)C)c(Cl)c4)cc3)nc12>>Cc1cccn2cc(-c3ccc(C[C@@H](CNC(=O)C(C)(C)N)NC(=O)c4ccc(OC(C)C)c(Cl)c4)cc3)nc12
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-be0cd13a66f44130ae9280cb4c5a7999
CN(C)CC(=O)O.Cc1cccn2cc(-c3ccc(C[C@@H](CN)NC(=O)c4ccc(OC(C)C)c(Cl)c4)cc3)nc12>>Cc1cccn2cc(-c3ccc(C[C@@H](CNC(=O)CN(C)C)NC(=O)c4ccc(OC(C)C)c(Cl)c4)cc3)nc12
NC[C@H](CC1=CC=C(C=C1)C=1N=C2N(C=CC=C2C)C1)NC(C1=CC(=C(C=C1)OC(C)C)Cl)=O.CN(CC(=O)O)C>>ClC=1C=C(C(=O)N[C@H](CNC(CN(C)C)=O)CC2=CC=C(C=C2)C=2N=C3N(C=CC=C3C)C2)C=CC1OC(C)C
O[C:17](=[O:18])[CH2:19][N:20]([CH3:21])[CH3:22].[CH3:1][c:2]1[cH:3][cH:4][cH:5][n:6]2[cH:7][c:8](-[c:9]3[cH:10][cH:11][c:12]([CH2:13][C@@H:14]([CH2:15][NH2:16])[NH:23][C:24](=[O:25])[c:26]4[cH:27][cH:28][c:29]([O:30][CH:31]([CH3:32])[CH3:33])[c:34]([Cl:35])[cH:36]4)[cH:37][cH:38]3)[n:39][c:40]12>>[CH3:1][c:2]1[cH:3][c...
CN(C)CC(=O)O.Cc1cccn2cc(-c3ccc(C[C@@H](CN)NC(=O)c4ccc(OC(C)C)c(Cl)c4)cc3)nc12
Cc1cccn2cc(-c3ccc(C[C@@H](CNC(=O)CN(C)C)NC(=O)c4ccc(OC(C)C)c(Cl)c4)cc3)nc12
null
null
null
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
O=C(NCCc1ccc(-c2cn3ccccc3n2)cc1)c1ccccc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[#7:4].[C:5]-[C:6]-[NH2;D1;+0:7]>>[#7:4]-[C:3]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:7]-[C:6]-[C:5]
null
[]
null
null
null
null
Following the procedure described above with N-((1S)-2-amino-1-{[4-(8-methylimidazo[1,2-a]pyridin-2-yl)phenyl]methyl}ethyl)-3-chloro-4-[(1-methylethyl)oxy]benzamide and N,N-dimethylglycine provided the title product as a white solid. ESMS [M+H]+: 563.2. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccn2ccnc2c1.c1ccccc1.c1ccccc1
HO-
null
null
null
CN(C)CC(=O)O.Cc1cccn2cc(-c3ccc(C[C@@H](CN)NC(=O)c4ccc(OC(C)C)c(Cl)c4)cc3)nc12>>Cc1cccn2cc(-c3ccc(C[C@@H](CNC(=O)CN(C)C)NC(=O)c4ccc(OC(C)C)c(Cl)c4)cc3)nc12
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-46065ad871d84bb58407ba5a331b2437
BrBr.CC(=O)c1ccc(I)cc1>>O=C(CBr)c1ccc(I)cc1
IC1=CC=C(C=C1)C(C)=O.BrBr>>BrCC(=O)C1=CC=C(C=C1)I
Br[Br:4].[O:1]=[C:2]([CH3:3])[c:5]1[cH:6][cH:7][c:8]([I:9])[cH:10][cH:11]1>>[O:1]=[C:2]([CH2:3][Br:4])[c:5]1[cH:6][cH:7][c:8]([I:9])[cH:10][cH:11]1
BrBr.CC(=O)c1ccc(I)cc1
O=C(CBr)c1ccc(I)cc1
null
null
O1CCOCC1
Functional Group Interconversion
Bromination
97ca6720945af5a02c450d33ec56e946521050f9771c27f9cfcb85f3477593f6
cb3e14519230141aa015a4cf9c960def3e60f01997e61621f62506924bfa15de
c1ccccc1
Br-[Br;H0;D1;+0:1].[CH3;D1;+0:2]-[C:3](=[O;D1;H0:4])-[c:5]>>[Br;H0;D1;+0:1]-[CH2;D2;+0:2]-[C:3](=[O;D1;H0:4])-[c:5]
null
[]
null
null
10
MINUTE
A solution of 1-(4-iodophenyl)ethanone (55.9 mmol) in dioxane (160 mL) was cooled to 10° C. Bromine (1.1 equiv, 61.6 mmol) was added dropwise to the reaction mixture. After 10 min, the cooling bath was removed and the reaction mixture was stirred at room temperature. After 1.5 h, the reaction mixture was concentrated i...
10.6084/m9.figshare.5104873.v1
null
Ketone
Primary halide
null
null
c1ccccc1
HBr
O1CCOCC1
null
0.166667
BrBr.CC(=O)c1ccc(I)cc1>O1CCOCC1>O=C(CBr)c1ccc(I)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-e80663ca80cd48d2beea8a417da76a1e
Cc1cccnc1N.O=C(CBr)c1ccc(I)cc1>>Cc1cccn2cc(-c3ccc(I)cc3)nc12
BrCC(=O)C1=CC=C(C=C1)I.NC1=NC=CC=C1C.C([O-])(O)=O.[Na+]>>IC1=CC=C(C=C1)C=1N=C2N(C=CC=C2C)C1
[CH3:1][c:2]1[cH:3][cH:4][cH:5][n:6][c:17]1[NH2:16].O=[C:8]([CH2:7]Br)[c:9]1[cH:10][cH:11][c:12]([I:13])[cH:14][cH:15]1>>[CH3:1][c:2]1[cH:3][cH:4][cH:5][n:6]2[cH:7][c:8](-[c:9]3[cH:10][cH:11][c:12]([I:13])[cH:14][cH:15]3)[n:16][c:17]12
Cc1cccnc1N.O=C(CBr)c1ccc(I)cc1
Cc1cccn2cc(-c3ccc(I)cc3)nc12
null
null
C(C)(C)O
Aromatic Heterocycle Formation
OtherReaction
98b9b4632b0457bc035e4a4d36e0a1658474c53cb0def2f4c4d097bbd0d48009
9e77d52183fdbe84f0d2ab96039aaf521caea9340e743bdc6436175f1a3bbdb6
c1ccc(-c2cn3ccccc3n2)cc1
Br-[CH2;D2;+0:1]-[C;H0;D3;+0:2](=O)-[c;H0;D3;+0:3](:[c:4]:[c:5]):[c:6]:[c:7].[NH2;D1;+0:8]-[c:9](:[c:10]):[n;H0;D2;+0:11]:[c:12]:[c:13]>>[c:5]:[c:4]:[c;H0;D3;+0:3](-[c;H0;D3;+0:2]1:[cH;D2;+0:1]:[n;H0;D3;+0:11](:[c:12]:[c:13]):[c:9](:[c:10]):[n;H0;D2;+0:8]:1):[c:6]:[c:7]
71
[{"value": 71.0, "product": "IC1=CC=C(C=C1)C=1N=C2N(C=CC=C2C)C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 70.5, "product": "IC1=CC=C(C=C1)C=1N=C2N(C=CC=C2C)C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
80
CELSIUS
null
null
A mixture of crude 2-bromo-1-(4-iodophenyl)ethanone (18.2 g), 2-amino-3-picoline (1.1 equiv, 61.6 mmol), and sodium bicarbonate (1.3 equiv, 72.8 mmol) in isopropanol (160 mL) was heated at 80° C. for 16 h. After concentrating the reaction mixture in vacuo, water (100 mL) was added and the resultant tan slurry was filte...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ketone.Primary amine
null
c1ccncc1
c1ccn2ccnc2c1
c1ccn2ccnc2c1.c1ccccc1
HBr
C(C)(C)O
80
null
Cc1cccnc1N.O=C(CBr)c1ccc(I)cc1>C(C)(C)O>Cc1cccn2cc(-c3ccc(I)cc3)nc12
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-057d255f7ce842748c57ff1c6fb2c454
CNOC.Cn1cc(-c2ccc(Br)cc2)nc1C(=O)O>>CON(C)C(=O)c1nc(-c2ccc(Br)cc2)cn1C
[Na].BrC1=CC=C(C=C1)C=1N=C(N(C1)C)C(=O)O.CN1CCOCC1.Cl.CNOC.ClC(=O)OCC(C)C>>BrC1=CC=C(C=C1)C=1N=C(N(C1)C)C(=O)N(OC)C
[CH3:1][O:2][NH:3][CH3:4].O[C:5](=[O:6])[c:7]1[n:8][c:9](-[c:10]2[cH:11][cH:12][c:13]([Br:14])[cH:15][cH:16]2)[cH:17][n:18]1[CH3:19]>>[CH3:1][O:2][N:3]([CH3:4])[C:5](=[O:6])[c:7]1[n:8][c:9](-[c:10]2[cH:11][cH:12][c:13]([Br:14])[cH:15][cH:16]2)[cH:17][n:18]1[CH3:19]
CNOC.Cn1cc(-c2ccc(Br)cc2)nc1C(=O)O
CON(C)C(=O)c1nc(-c2ccc(Br)cc2)cn1C
null
null
C(Cl)Cl
Acylation
Acylation of Nitrogen Nucleophiles by Carboxylic Acids
ac72df6259d5d7baee7abdbd4706ef4b4627f86ead9dc94f0cefcfcb37c21def
c5e4172490b2731ba9322b68af56376edadc31ce0bb9a3dfdea23a1817a852fd
c1ccc(-c2c[nH]cn2)cc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3]1:[#7;a:4]:[c:5]:[c:6]:[#7;a:7]:1-[C;D1;H3:8].[C;D1;H3:9]-[#8:10]-[NH;D2;+0:11]-[C;D1;H3:12]>>[C;D1;H3:8]-[#7;a:7]1:[c:6]:[c:5]:[#7;a:4]:[c:3]:1-[C;H0;D3;+0:1](=[O;D1;H0:2])-[N;H0;D3;+0:11](-[C;D1;H3:12])-[#8:10]-[C;D1;H3:9]
32
[{"value": 32.0, "product": "BrC1=CC=C(C=C1)C=1N=C(N(C1)C)C(=O)N(OC)C", "details": "PERCENTYIELD", "is_desired": false}]
-15
CELSIUS
15
MINUTE
To a solution of ethyl 4-(4-bromophenyl)-1-methyl-1H-imidazole-2-carboxylate (1.66 g, 5.37 mmol) in MeOH (38 mL) was added 1N NaOH solution (19 mL). The reaction turned cloudy white and was stirred at room temperature for 30 minutes. The reaction mixture was concentrated in vacuo and pumped under high vacuum overnight ...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Secondary amine
Tertiary amide
null
null
c1cnc[nH]1.c1ccccc1
HO-
C(Cl)Cl
-15
0.25
CNOC.Cn1cc(-c2ccc(Br)cc2)nc1C(=O)O>C(Cl)Cl>CON(C)C(=O)c1nc(-c2ccc(Br)cc2)cn1C
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-71375fbc69e444e4a55da1804283eee2
CC(C)(C)OC(=O)CC[C@H](CI)NC(=O)OC(C)(C)C.Cc1cccn2cc(-c3ccc(I)cc3)nc12>>Cc1cccn2cc(-c3ccc(C[C@@H](CCC(=O)OC(C)(C)C)NC(=O)OC(C)(C)C)cc3)nc12
BrCCBr.Cl[Si](C)(C)C.CC(C)(C)OC(=O)N[C@H](CCC(=O)OC(C)(C)C)CI.C1(=C(C=CC=C1)P(C1=C(C=CC=C1)C)C1=C(C=CC=C1)C)C.IC1=CC=C(C=C1)C=1N=C2N(C=CC=C2C)C1>>CC(C)(C)OC(=O)N[C@H](CCC(=O)OC(C)(C)C)CC1=CC=C(C=C1)C=1N=C2N(C=CC=C2C)C1
I[CH2:13][C@@H:14]([CH2:15][CH2:16][C:17](=[O:18])[O:19][C:20]([CH3:21])([CH3:22])[CH3:23])[NH:24][C:25](=[O:26])[O:27][C:28]([CH3:29])([CH3:30])[CH3:31].I[c:12]1[cH:11][cH:10][c:9](-[c:8]2[cH:7][n:6]3[cH:5][cH:4][cH:3][c:2]([CH3:1])[c:35]3[n:34]2)[cH:33][cH:32]1>>[CH3:1][c:2]1[cH:3][cH:4][cH:5][n:6]2[cH:7][c:8](-[c:9]...
CC(C)(C)OC(=O)CC[C@H](CI)NC(=O)OC(C)(C)C.Cc1cccn2cc(-c3ccc(I)cc3)nc12
Cc1cccn2cc(-c3ccc(C[C@@H](CCC(=O)OC(C)(C)C)NC(=O)OC(C)(C)C)cc3)nc12
null
[Zn].C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd]
CN(C)C=O.CCOC(=O)C
C-C Coupling
Negishi
530a9bd1eaaebd54d09786b6168a1d1d89df12b3fda60e0c00afadb98df85946
84e12b0159f1d183204538a38a0b22f090552039c6c4b4ca4a95700e436c4e5e
c1ccc(-c2cn3ccccc3n2)cc1
I-[CH2;D2;+0:1]-[C:2](-[C:3])-[#7:4]-[C:5](=[O;D1;H0:6])-[#8:7]-[C:8](-[C;D1;H3:9])(-[C;D1;H3:10])-[C;D1;H3:11].I-[c;H0;D3;+0:12](:[c:13]:[c:14]):[c:15]:[c:16]>>[C:3]-[C:2](-[#7:4]-[C:5](=[O;D1;H0:6])-[#8:7]-[C:8](-[C;D1;H3:9])(-[C;D1;H3:10])-[C;D1;H3:11])-[CH2;D2;+0:1]-[c;H0;D3;+0:12](:[c:13]:[c:14]):[c:15]:[c:16]
90
[{"value": 90.0, "product": "CC(C)(C)OC(=O)N[C@H](CCC(=O)OC(C)(C)C)CC1=CC=C(C=C1)C=1N=C2N(C=CC=C2C)C1", "details": "PERCENTYIELD", "is_desired": false}]
100
CELSIUS
15
MINUTE
A flask containing zinc dust (6.0 equiv, 325 mesh, Strem) was heated with a heat gun while evacuating and filling with nitrogen (3 times). Under nitrogen, degassed DMF (14 mL) was added via syringe followed by 1,2-dibromoethane (0.35 equiv). The grey reaction mixture was stirred in an oil bath at 100° C. for 15 minutes...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary halide
null
c1ccccc1
c1ccccc1
c1ccn2ccnc2c1.c1ccccc1
I-
[Zn].C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd].CN(C)C=O.CCOC(=O)C
100
0.25
CC(C)(C)OC(=O)CC[C@H](CI)NC(=O)OC(C)(C)C.Cc1cccn2cc(-c3ccc(I)cc3)nc12>[Zn].C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd].CN(C)C=O.CCOC(=O)C>Cc1cccn2cc(-c3ccc(C[C@@H](CCC(=O)OC(C)(C)C)NC(=O)OC(C)(C)C)cc3)nc12
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-d72ee98388eb46d4be26dc716f355c6d
CC(C)Oc1ccc(C(=O)Oc2c(F)c(F)c(F)c(F)c2F)cc1Cl.Cc1cccn2cc(-c3ccc(C[C@@H](CCC(=O)OC(C)(C)C)NC(=O)OC(C)(C)C)cc3)nc12>>Cc1cccn2cc(-c3ccc(C[C@@H](CCC(=O)O)NC(=O)c4ccc(OC(C)C)c(Cl)c4)cc3)nc12
C(C)(C)NC(C)C.CC(C)(C)OC(=O)N[C@H](CCC(=O)OC(C)(C)C)CC1=CC=C(C=C1)C=1N=C2N(C=CC=C2C)C1.FC(C(=O)O)(F)F.ClC=1C=C(C(=O)OC2=C(C(=C(C(=C2F)F)F)F)F)C=CC1OC(C)C.C(C)[SiH](CC)CC>>ClC=1C=C(C=CC1OC(C)C)C(=O)N[C@H](CCC(=O)O)CC1=CC=C(C=C1)C=1N=C2N(C=CC=C2C)C1
Fc1c(F)c(F)c(O[C:21](=[O:22])[c:23]2[cH:24][cH:25][c:26]([O:27][CH:28]([CH3:29])[CH3:30])[c:31]([Cl:32])[cH:33]2)c(F)c1F.CC(C)(C)OC(=O)[NH:20][C@@H:14]([CH2:13][c:12]1[cH:11][cH:10][c:9](-[c:8]2[cH:7][n:6]3[cH:5][cH:4][cH:3][c:2]([CH3:1])[c:37]3[n:36]2)[cH:35][cH:34]1)[CH2:15][CH2:16][C:17](=[O:18])[O:19]C(C)(C)C>>[CH3...
CC(C)Oc1ccc(C(=O)Oc2c(F)c(F)c(F)c(F)c2F)cc1Cl.Cc1cccn2cc(-c3ccc(C[C@@H](CCC(=O)OC(C)(C)C)NC(=O)OC(C)(C)C)cc3)nc12
Cc1cccn2cc(-c3ccc(C[C@@H](CCC(=O)O)NC(=O)c4ccc(OC(C)C)c(Cl)c4)cc3)nc12
null
null
C(Cl)Cl
Protection
OtherReaction
9b3d2ad13665a37c756c1725995b29ed925d85c55a22d6291c1d088613f27582
545d38d838a170ec25ef129ae973a0f72fde2e06b47ea8db25c0a3c0098b77bf
O=C(NCCc1ccc(-c2cn3ccccc3n2)cc1)c1ccccc1
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[C:2](-[C:3])-[C:4]-[C:5]-[C:6](=[O;D1;H0:7])-[O;H0;D2;+0:8]-C(-C)(-C)-C.F-c1:c(-F):c(-F):c(-O-[C;H0;D3;+0:9](=[O;D1;H0:10])-[c:11](:[c:12]):[c:13]):c(-F):c:1-F>>[C:3]-[C:2](-[C:4]-[C:5]-[C:6](=[O;D1;H0:7])-[OH;D1;+0:8])-[NH;D2;+0:1]-[C;H0;D3;+0:9](=[O;D1;H0:10])-[c:11](:[c:12]):[c:13]
61
[{"value": 61.0, "product": "ClC=1C=C(C=CC1OC(C)C)C(=O)N[C@H](CCC(=O)O)CC1=CC=C(C=C1)C=1N=C2N(C=CC=C2C)C1", "details": "PERCENTYIELD", "is_desired": false}]
null
null
45
MINUTE
To a solution of 1,1-dimethylethyl (4R)-4-(([(1,1-dimethylethyl)oxy]carbonyl}amino)-5-[4-(8-methylimidazo[1,2-a]pyridin-2-yl)phenyl]pentanoate (1.35 g, 2.82 mmol) in CH2Cl2 (14 mL) was added trifluoroacetic acid (10 mL) followed by triethylsilane (2.5 equiv, 7.04 mmol). The reaction was stirred for 45 minutes at room t...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic halide.Aromatic halide.Aromatic halide.Aromatic halide.Carbamic ester.Ester.Ester.Ether.Boc.Boc
Carboxylic acid.Secondary amide
c1ccccc1
null
c1ccn2ccnc2c1.c1ccccc1.c1ccccc1
HF
C(Cl)Cl
null
0.75
CC(C)Oc1ccc(C(=O)Oc2c(F)c(F)c(F)c(F)c2F)cc1Cl.Cc1cccn2cc(-c3ccc(C[C@@H](CCC(=O)OC(C)(C)C)NC(=O)OC(C)(C)C)cc3)nc12>C(Cl)Cl>Cc1cccn2cc(-c3ccc(C[C@@H](CCC(=O)O)NC(=O)c4ccc(OC(C)C)c(Cl)c4)cc3)nc12
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-9b006af1c25e4eab9109a00f18f384e4
CON(C)C(=O)c1nc(-c2ccc(C[C@@H](CCC(=O)O)NC(=O)c3ccc(OC(C)C)c(Cl)c3)cc2)cn1C>>CC(=O)c1nc(-c2ccc(C[C@@H](CCC(=O)O)NC(=O)c3ccc(OC(C)C)c(Cl)c3)cc2)cn1C
ClC=1C=C(C=CC1OC(C)C)C(=O)N[C@H](CCC(=O)O)CC1=CC=C(C=C1)C=1N=C(N(C1)C)C(=O)N(OC)C.C[Mg]Br>>C(C)(=O)C=1N(C=C(N1)C1=CC=C(C=C1)C[C@@H](CCC(=O)O)NC(=O)C1=CC(=C(C=C1)OC(C)C)Cl)C
CON(C)[C:2](=[O:3])[c:4]1[n:5][c:6](-[c:7]2[cH:8][cH:9][c:10]([CH2:11][C@@H:12]([CH2:13][CH2:14][C:15](=[O:16])[OH:17])[NH:18][C:19](=[O:20])[c:21]3[cH:22][cH:23][c:24]([O:25][CH:26]([CH3:27])[CH3:28])[c:29]([Cl:30])[cH:31]3)[cH:32][cH:33]2)[cH:34][n:35]1[CH3:36]>>[CH3:1][C:2](=[O:3])[c:4]1[n:5][c:6](-[c:7]2[cH:8][cH:9...
CON(C)C(=O)c1nc(-c2ccc(C[C@@H](CCC(=O)O)NC(=O)c3ccc(OC(C)C)c(Cl)c3)cc2)cn1C
CC(=O)c1nc(-c2ccc(C[C@@H](CCC(=O)O)NC(=O)c3ccc(OC(C)C)c(Cl)c3)cc2)cn1C
null
null
C1CCOC1
Functional Group Interconversion
OtherReaction
0e1b501f4aadb0e84ffc93b33216cc37dfe617cb6c3e325779c58539a7f5c4e4
af85307a4412ed48cedcfde84079732215472ffbe274bdc1dc12e9979d5c5e06
O=C(NCCc1ccc(-c2c[nH]cn2)cc1)c1ccccc1
C-O-N(-C)-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3]1:[#7;a:4]:[c:5]:[c:6]:[#7;a:7]:1-[C;D1;H3:8]>>[C;D1;H3:9]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3]1:[#7;a:4]:[c:5]:[c:6]:[#7;a:7]:1-[C;D1;H3:8]
null
[]
0
CELSIUS
30
MINUTE
To a solution of crude (4R)-4-[({3-chloro-4-[(1-methylethyl)oxy]phenyl}carbonyl)amino]-5-[4-(1-methyl-2-{[methyl(methyloxy)amino]carbonyl}-1H-imidazol-4-yl)phenyl]pentanoic acid (3.18 mmol) in anhydrous THF (16 mL) under nitrogen at 0° C. was added methylmagnesium bromide (10.6 mL, 10 equiv, 3.0 M in ether) dropwise by...
10.6084/m9.figshare.5104873.v1
null
Tertiary amide
Ketone
null
null
c1cnc[nH]1.c1ccccc1.c1ccccc1
HO-
C1CCOC1
0
0.5
CON(C)C(=O)c1nc(-c2ccc(C[C@@H](CCC(=O)O)NC(=O)c3ccc(OC(C)C)c(Cl)c3)cc2)cn1C>C1CCOC1>CC(=O)c1nc(-c2ccc(C[C@@H](CCC(=O)O)NC(=O)c3ccc(OC(C)C)c(Cl)c3)cc2)cn1C
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-8c7ddc9d030f47529d456ea9745fa805
CC(=O)c1nc(-c2ccc(C[C@@H](CCO)NC(=O)c3ccc(OC(C)C)c(Cl)c3)cc2)cn1C.COP(=O)(Cl)OC>>COP(=O)(OC)OCC[C@H](Cc1ccc(-c2cn(C)c(C(C)=O)n2)cc1)NC(=O)c1ccc(OC(C)C)c(Cl)c1
CCOC(=O)C.CO.P(=O)(OC)(OC)Cl.C(C)(=O)C=1N(C=C(N1)C1=CC=C(C=C1)C[C@@H](CCO)NC(C1=CC(=C(C=C1)OC(C)C)Cl)=O)C.P(=O)(OC)(OC)Cl>>P(=O)(OCC[C@H](CC1=CC=C(C=C1)C=1N=C(N(C1)C)C(C)=O)NC(=O)C1=CC(=C(C=C1)OC(C)C)Cl)(OC)OC
[OH:7][CH2:8][CH2:9][C@H:10]([CH2:11][c:12]1[cH:13][cH:14][c:15](-[c:16]2[cH:17][n:18]([CH3:19])[c:20]([C:21]([CH3:22])=[O:23])[n:24]2)[cH:25][cH:26]1)[NH:27][C:28](=[O:29])[c:30]1[cH:31][cH:32][c:33]([O:34][CH:35]([CH3:36])[CH3:37])[c:38]([Cl:39])[cH:40]1.Cl[P:3]([O:2][CH3:1])(=[O:4])[O:5][CH3:6]>>[CH3:1][O:2][P:3](=[...
CC(=O)c1nc(-c2ccc(C[C@@H](CCO)NC(=O)c3ccc(OC(C)C)c(Cl)c3)cc2)cn1C.COP(=O)(Cl)OC
COP(=O)(OC)OCC[C@H](Cc1ccc(-c2cn(C)c(C(C)=O)n2)cc1)NC(=O)c1ccc(OC(C)C)c(Cl)c1
null
CN(C)C=1C=CN=CC1.CN(C)C=1C=CN=CC1
C(Cl)Cl
Miscellaneous
OtherReaction
f468963cd150795c559ea97eef415e4c6e817d5e41b8e41bf56e6fc6478dce9b
0450d2d3d6169ebd913d75de6102597ba0029b73d4e4cd2ca50ccc23bda73392
O=C(NCCc1ccc(-c2c[nH]cn2)cc1)c1ccccc1
Cl-[P;H0;D4;+0:1](=[O;D1;H0:2])(-[#8:3]-[C;D1;H3:4])-[#8:5]-[C;D1;H3:6].[C:7]-[C:8]-[OH;D1;+0:9]>>[C:7]-[C:8]-[O;H0;D2;+0:9]-[P;H0;D4;+0:1](=[O;D1;H0:2])(-[#8:3]-[C;D1;H3:4])-[#8:5]-[C;D1;H3:6]
77.1
[{"value": 77.0, "product": "P(=O)(OCC[C@H](CC1=CC=C(C=C1)C=1N=C(N(C1)C)C(C)=O)NC(=O)C1=CC(=C(C=C1)OC(C)C)Cl)(OC)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 77.1, "product": "P(=O)(OCC[C@H](CC1=CC=C(C=C1)C=1N=C(N(C1)C)C(C)=O)NC(=O)C1=CC(=C(C=C1)OC(C)C)Cl)(OC)OC", "details": "CALCULATEDPERCENTYIELD",...
null
null
30
MINUTE
To a solution of N-((1S)-1-{[4-(2-acetyl-1-methyl-1H-imidazol-4-yl)phenyl]methyl}-3-hydroxypropyl)-3-chloro-4-[(1-methylethyl)oxy]benzamide (500 mg, 1.04 mmol) in dry CH2Cl2 (10 mL) under N2, was added dimethyl chlorophosphate (748 mg, 5.18 mmol) followed by DMAP (660 mg, 5.41 mmol) at rt. After 30 min, TLC (95:5 EtOAc...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol
null
null
null
c1ccccc1.c1c[nH]cn1.c1ccccc1
HCl
CN(C)C=1C=CN=CC1.CN(C)C=1C=CN=CC1.C(Cl)Cl
null
0.5
CC(=O)c1nc(-c2ccc(C[C@@H](CCO)NC(=O)c3ccc(OC(C)C)c(Cl)c3)cc2)cn1C.COP(=O)(Cl)OC>CN(C)C=1C=CN=CC1.CN(C)C=1C=CN=CC1.C(Cl)Cl>COP(=O)(OC)OCC[C@H](Cc1ccc(-c2cn(C)c(C(C)=O)n2)cc1)NC(=O)c1ccc(OC(C)C)c(Cl)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a364b73772ed4c06a987b41907701bd9
COP(=O)(OC)OCC[C@H](Cc1ccc(-c2cn(C)c(C(C)=O)n2)cc1)NC(=O)c1ccc(OC(C)C)c(Cl)c1>>CC(=O)c1nc(-c2ccc(C[C@@H](CCOP(=O)(O)O)NC(=O)c3ccc(OC(C)C)c(Cl)c3)cc2)cn1C
P(=O)(OCC[C@H](CC1=CC=C(C=C1)C=1N=C(N(C1)C)C(C)=O)NC(=O)C1=CC(=C(C=C1)OC(C)C)Cl)(OC)OC>>P(=O)(OCC[C@H](CC1=CC=C(C=C1)C=1N=C(N(C1)C)C(C)=O)NC(=O)C1=CC(=C(C=C1)OC(C)C)Cl)(O)O
C[O:18][P:16]([O:15][CH2:14][CH2:13][C@H:12]([CH2:11][c:10]1[cH:9][cH:8][c:7](-[c:6]2[n:5][c:4]([C:2]([CH3:1])=[O:3])[n:37]([CH3:38])[cH:36]2)[cH:35][cH:34]1)[NH:20][C:21](=[O:22])[c:23]1[cH:24][cH:25][c:26]([O:27][CH:28]([CH3:29])[CH3:30])[c:31]([Cl:32])[cH:33]1)(=[O:17])[O:19]C>>[CH3:1][C:2](=[O:3])[c:4]1[n:5][c:6](-...
COP(=O)(OC)OCC[C@H](Cc1ccc(-c2cn(C)c(C(C)=O)n2)cc1)NC(=O)c1ccc(OC(C)C)c(Cl)c1
CC(=O)c1nc(-c2ccc(C[C@@H](CCOP(=O)(O)O)NC(=O)c3ccc(OC(C)C)c(Cl)c3)cc2)cn1C
null
null
CC(=O)O.Br
Deprotection
OtherReaction
b49938033a0fd56e13d2f970a169ac47cce77c866363ab153142c53fe34d7d82
ecac314cca8b931f5bfebb391dc97e333d1eca60b386dbe5c9a60f4d76cdb838
O=C(NCCc1ccc(-c2c[nH]cn2)cc1)c1ccccc1
C-[O;H0;D2;+0:1]-[#15:2](-[#8:3])(=[O;D1;H0:4])-[O;H0;D2;+0:5]-C>>[#8:3]-[#15:2](=[O;D1;H0:4])(-[OH;D1;+0:1])-[OH;D1;+0:5]
19
[{"value": 19.0, "product": "P(=O)(OCC[C@H](CC1=CC=C(C=C1)C=1N=C(N(C1)C)C(C)=O)NC(=O)C1=CC(=C(C=C1)OC(C)C)Cl)(O)O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 18.5, "product": "P(=O)(OCC[C@H](CC1=CC=C(C=C1)C=1N=C(N(C1)C)C(C)=O)NC(=O)C1=CC(=C(C=C1)OC(C)C)Cl)(O)O", "details": "CALCULATEDPERCENTYIELD", "is...
60
CELSIUS
8
HOUR
A yellow solution of (3S)-4-[4-(2-acetyl-1-methyl-1H-imidazol-4-yl)phenyl]-3-[({3-chloro-4-[(1-methylethyl)oxy]phenyl}carbonyl)amino]butyl dimethyl phosphate (475 mg, 0.804 mmol) in 30% HBr in AcOH was placed in a pre-heated (60° C.) bath for 10 min, then immediately allowed to cool to rt. The reaction mixture was conc...
10.6084/m9.figshare.5104873.v1
null
null
Phosphate ester
null
null
c1cnc[nH]1.c1ccccc1.c1ccccc1
Other
CC(=O)O.Br
60
8
COP(=O)(OC)OCC[C@H](Cc1ccc(-c2cn(C)c(C(C)=O)n2)cc1)NC(=O)c1ccc(OC(C)C)c(Cl)c1>CC(=O)O.Br>CC(=O)c1nc(-c2ccc(C[C@@H](CCOP(=O)(O)O)NC(=O)c3ccc(OC(C)C)c(Cl)c3)cc2)cn1C
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-5699166f64e5406d837e82fe89aebc36
CC(C)Oc1ccc(C(=O)N[C@H](CCO)Cc2ccc(-c3cn4cccc(Br)c4n3)cc2)cc1C#N.Cc1noc(C)c1B(O)O>>Cc1noc(C)c1-c1cccn2cc(-c3ccc(C[C@@H](CCO)NC(=O)c4ccc(OC(C)C)c(C#N)c4)cc3)nc12
BrC=1C=2N(C=CC1)C=C(N2)C2=CC=C(C=C2)C[C@@H](CCO)NC(C2=CC(=C(C=C2)OC(C)C)C#N)=O.CC1=NOC(=C1B(O)O)C.C(=O)([O-])[O-].[K+].[K+]>>C(#N)C=1C=C(C(=O)N[C@H](CCO)CC2=CC=C(C=C2)C=2N=C3N(C=CC=C3C=3C(=NOC3C)C)C2)C=CC1OC(C)C
Br[c:8]1[cH:9][cH:10][cH:11][n:12]2[cH:13][c:14](-[c:15]3[cH:16][cH:17][c:18]([CH2:19][C@@H:20]([CH2:21][CH2:22][OH:23])[NH:24][C:25](=[O:26])[c:27]4[cH:28][cH:29][c:30]([O:31][CH:32]([CH3:33])[CH3:34])[c:35]([C:36]#[N:37])[cH:38]4)[cH:39][cH:40]3)[n:41][c:42]12.OB(O)[c:7]1[c:2]([CH3:1])[n:3][o:4][c:5]1[CH3:6]>>[CH3:1]...
CC(C)Oc1ccc(C(=O)N[C@H](CCO)Cc2ccc(-c3cn4cccc(Br)c4n3)cc2)cc1C#N.Cc1noc(C)c1B(O)O
Cc1noc(C)c1-c1cccn2cc(-c3ccc(C[C@@H](CCO)NC(=O)c4ccc(OC(C)C)c(C#N)c4)cc3)nc12
null
null
CN(C)C=O
C-C Coupling
Suzuki coupling with boronic acids
a733f0cb9ddc6219931356bfd9d2fb02959abad7e10e6cfb4c00073a10f09758
08d2969413ef1a2cd5b43667268ba178160c7b55545bf48018e31f2b019632ec
O=C(NCCc1ccc(-c2cn3cccc(-c4cnoc4)c3n2)cc1)c1ccccc1
Br-[c;H0;D3;+0:1]1:[c:2]:[c:3]:[c:4]:[#7;a:5]2:[c:6]:[c:7]:[#7;a:8]:[c:9]:2:1.O-B(-O)-[c;H0;D3;+0:10]1:[c:11](-[C;D1;H3:12]):[#7;a:13]:[#8;a:14]:[c:15]:1-[C;D1;H3:16]>>[C;D1;H3:12]-[c:11]1:[#7;a:13]:[#8;a:14]:[c:15](-[C;D1;H3:16]):[c;H0;D3;+0:10]:1-[c;H0;D3;+0:1]1:[c:2]:[c:3]:[c:4]:[#7;a:5]2:[c:6]:[c:7]:[#7;a:8]:[c:9]:...
22
[{"value": 22.0, "product": "C(#N)C=1C=C(C(=O)N[C@H](CCO)CC2=CC=C(C=C2)C=2N=C3N(C=CC=C3C=3C(=NOC3C)C)C2)C=CC1OC(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 21.8, "product": "C(#N)C=1C=C(C(=O)N[C@H](CCO)CC2=CC=C(C=C2)C=2N=C3N(C=CC=C3C=3C(=NOC3C)C)C2)C=CC1OC(C)C", "details": "CALCULATEDPERCENTYIELD",...
100
CELSIUS
22
HOUR
To a solution of N-((1S)-1-{[4-(8-bromoimidazo[1,2-a]pyridin-2-yl)phenyl]methyl)-3-hydroxypropyl)-3-cyano-4-[(1-methylethyl)oxy]benzamide (200 mg, 0.366 mmol) in dry DMF (2 mL) were added 3,5-dimethyl-isoxazole-4-boronic acid (63 mg, 0.439 mmol), tetrakistriphenylphosphine palladium(0) (21 mg, 0.018 mmol) and 2.0 M aqu...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Boronic acid
null
c1ccn2ccnc2c1.c1cnoc1
c1cnoc1.c1ccn2ccnc2c1
c1cnoc1.c1ccn2ccnc2c1.c1ccccc1.c1ccccc1
HBr.B
CN(C)C=O
100
22
CC(C)Oc1ccc(C(=O)N[C@H](CCO)Cc2ccc(-c3cn4cccc(Br)c4n3)cc2)cc1C#N.Cc1noc(C)c1B(O)O>CN(C)C=O>Cc1noc(C)c1-c1cccn2cc(-c3ccc(C[C@@H](CCO)NC(=O)c4ccc(OC(C)C)c(C#N)c4)cc3)nc12
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-c822f19a093c49beb1311b4299041411
NC(=O)[C@@H](N)Cc1ccc(O)cc1>>c1ccc2[nH]cnc2c1
N[C@@H](CC1=CC=C(C=C1)O)C(=O)N.Cl.C(C)N(CC)CC.FC(C(=O)OC1=C(C(=C(C(=C1F)F)F)F)F)(F)F>>N1=CNC2=C1C=CC=C2
O=[C:6]([C@H](C[c:4]1[cH:3][cH:2][c:1](O)[cH:9][cH:8]1)[NH2:5])[NH2:7]>>[cH:1]1[cH:2][cH:3][c:4]2[nH:5][cH:6][n:7][c:8]2[cH:9]1
NC(=O)[C@@H](N)Cc1ccc(O)cc1
c1ccc2[nH]cnc2c1
null
null
null
Aromatic Heterocycle Formation
OtherReaction
8122077837d574c1833e90acf44c3fd8221ff4c194f4f1f3e2c3974049e231a7
073fb5aa4cd15969a74799a193e5a035fb3eef58e311c8a52c655b67e20989e7
c1ccc2[nH]cnc2c1
O-[c;H0;D3;+0:1]1:[c:2]:[c:3]:[c;H0;D3;+0:4](-C-[C@H](-[NH2;D1;+0:5])-[C;H0;D3;+0:6](=O)-[NH2;D1;+0:7]):[cH;D2;+0:8]:[c:9]:1>>[c:2]1:[c:3]:[c;H0;D3;+0:4]2:[nH;D2;+0:5]:[cH;D2;+0:6]:[n;H0;D2;+0:7]:[c;H0;D3;+0:8]:2:[c:9]:[cH;D2;+0:1]:1
193.1
[{"value": 50.0, "product": "N1=CNC2=C1C=CC=C2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 193.1, "product": "N1=CNC2=C1C=CC=C2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
5
MINUTE
To a 0° C. crude solution of compound 2 (4.1 g, 15.34 mmol) and triethylamine (6.4 mL, 46.02 mmol) in dicholoromethane (200 mL) was added pentafluorophenyl trifluoroacetate (6.35 mL, 36.82 mmol) via syringe over 3 min. After another 5 min, the ice bath was removed and the reaction mixture stirred while warming to room ...
10.6084/m9.figshare.5104873.v1
null
Primary amide.Aromatic alcohol.Primary amine
null
c1ccccc1
c1ccc2[nH]cnc2c1
c1ccc2[nH]cnc2c1
HO-
null
null
0.083333
NC(=O)[C@@H](N)Cc1ccc(O)cc1>>c1ccc2[nH]cnc2c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-d3c146894f7c4d3bbbe43f82e2c786cc
COC(=O)c1ccc(O)cc1.ClI>>COC(=O)c1ccc(O)c(I)c1
OC1=CC=C(C(=O)OC)C=C1.ICl>>OC1=C(C=C(C(=O)OC)C=C1)I
[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([OH:9])[cH:10][cH:12]1.Cl[I:11]>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([OH:9])[c:10]([I:11])[cH:12]1
COC(=O)c1ccc(O)cc1.ClI
COC(=O)c1ccc(O)c(I)c1
null
null
CC(=O)O.C(C)(=O)O
Functional Group Interconversion
OtherReaction
f6effe61353895b318215d8bd9b6bb1105cafbf7be8c217d748df587260b32c3
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
c1ccccc1
Cl-[I;H0;D1;+0:1].[#8:2]-[C:3](=[O;D1;H0:4])-[c:5]:[c:6]:[cH;D2;+0:7]:[c:8](-[O;D1;H1:9]):[c:10]>>[#8:2]-[C:3](=[O;D1;H0:4])-[c:5]:[c:6]:[c;H0;D3;+0:7](-[I;H0;D1;+0:1]):[c:8](-[O;D1;H1:9]):[c:10]
90.3
[{"value": 90.3, "product": "OC1=C(C=C(C(=O)OC)C=C1)I", "details": "PERCENTYIELD", "is_desired": false}]
65
CELSIUS
5
HOUR
Methyl 4-hydroxybenzoate (35.5 g, 0.233 mol) was dissolved in 200 mL of acetic acid, and the stirred mixture was warmed to 65° C. A solution of ICl (37.8 g, 0.233 mol) in 50 mL of AcOH was added dropwise over 40 min. The mixture was stirred at 65° C. for 5 h and then stirred an additional 16 h at room temperature. The ...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ccccc1
c1ccccc1
c1ccccc1
HCl
CC(=O)O.C(C)(=O)O
65
5
COC(=O)c1ccc(O)cc1.ClI>CC(=O)O.C(C)(=O)O>COC(=O)c1ccc(O)c(I)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a1663a1f970f469990f7e8f069bbcfb4
COC(=O)c1ccc(O)c(I)c1>>COC(=O)c1ccc(O)c(C#N)c1
OC1=C(C=C(C(=O)OC)C=C1)I.C(#N)[Cu].[C-]#N.[Na+]>>C(#N)C=1C=C(C(=O)OC)C=CC1O
I[c:10]1[c:8]([OH:9])[cH:7][cH:6][c:5]([C:3]([O:2][CH3:1])=[O:4])[cH:13]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([OH:9])[c:10]([C:11]#[N:12])[cH:13]1
COC(=O)c1ccc(O)c(I)c1
COC(=O)c1ccc(O)c(C#N)c1
null
null
CN(C)C=O
Miscellaneous
OtherReaction
3ae4da8b7f110de99cf8afc091b6f0c8540050148e425770f8030bce1480042c
73a96fe5e833259ca394a42f82d6cc2ee7231bcde92d95030d2893b90c3fef76
c1ccccc1
I-[c;H0;D3;+0:1](:[c:2]:[c:3]-[C:4](-[#8:5])=[O;D1;H0:6]):[c:7](-[O;D1;H1:8]):[c:9]>>[#8:5]-[C:4](=[O;D1;H0:6])-[c:3]:[c:2]:[c;H0;D3;+0:1](-[C:10]#[N;D1;H0:11]):[c:7](-[O;D1;H1:8]):[c:9]
101.6
[{"value": 100.0, "product": "C(#N)C=1C=C(C(=O)OC)C=CC1O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 101.6, "product": "C(#N)C=1C=C(C(=O)OC)C=CC1O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
105
CELSIUS
18
HOUR
28 g (0.1 mol) of methyl 4-hydroxy-3-iodobenzoate 2 dissolved in 100 mL of DMF was treated with 9.92 g (0.11 mol) of CuCN and 0.49 g (0.11 mol) of NaCN. The system was flushed with nitrogen after which the mixture warmed to 105° C. and stirred to 18 h. The mixture was allowed to cool to room temperature, and any precip...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
Nitrile
c1ccccc1
c1ccccc1
c1ccccc1
I-
CN(C)C=O
105
18
COC(=O)c1ccc(O)c(I)c1>CN(C)C=O>COC(=O)c1ccc(O)c(C#N)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-fca985d0f37c4db894293c1c47a3ff43
CC(C)Br.COC(=O)c1ccc(O)c(C#N)c1>>COC(=O)c1ccc(OC(C)C)c(C#N)c1
C(#N)C=1C=C(C(=O)OC)C=CC1O.BrC(C)C.C([O-])([O-])=O.[K+].[K+]>>C(#N)C=1C=C(C(=O)OC)C=CC1OC(C)C
Br[CH:10]([CH3:11])[CH3:12].[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([OH:9])[c:13]([C:14]#[N:15])[cH:16]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([O:9][CH:10]([CH3:11])[CH3:12])[c:13]([C:14]#[N:15])[cH:16]1
CC(C)Br.COC(=O)c1ccc(O)c(C#N)c1
COC(=O)c1ccc(OC(C)C)c(C#N)c1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
bff4876be49b448135c783dd3eeeb68ab3cc5bdc91beadda8a9095106cd5c747
cf768afb66ed5041aefdce1fa6d1e40995a1ab7c4b4a4ca47544fe49ee1e629f
c1ccccc1
Br-[CH;D3;+0:1](-[C;D1;H3:2])-[C;D1;H3:3].[OH;D1;+0:4]-[c:5](:[c:6]):[c:7]>>[C;D1;H3:2]-[CH;D3;+0:1](-[C;D1;H3:3])-[O;H0;D2;+0:4]-[c:5](:[c:6]):[c:7]
99
[{"value": 99.0, "product": "C(#N)C=1C=C(C(=O)OC)C=CC1OC(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 93.5, "product": "C(#N)C=1C=C(C(=O)OC)C=CC1OC(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
90
CELSIUS
8
HOUR
Methyl 3-cyano-4-hydroxybenzoate 3 (18 g, 0.1 mol) was dissolved in 100 mL of DMF and treated with 14.2 mL (0.15 mol) of 2-bromopropane and 41.9 g (0.3 mol) of anhydrous potassium carbonate. The system was flushed with nitrogen, and the mixture was heated to 90° C. with stirring overnight. After cooling to room tempera...
10.6084/m9.figshare.5104873.v1
null
Secondary halide.Aromatic alcohol
Ether
null
null
c1ccccc1
HBr
CN(C)C=O
90
8
CC(C)Br.COC(=O)c1ccc(O)c(C#N)c1>CN(C)C=O>COC(=O)c1ccc(OC(C)C)c(C#N)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-de925e9d139e4a2dbba1bff9dc6f6f3c
COC(=O)c1ccc(OC(C)C)c(C#N)c1.O=C(Oc1c(F)c(F)c(F)c(F)c1F)C(F)(F)F>>CC(C)Oc1ccc(C(=O)Oc2c(F)c(F)c(F)c(F)c2F)cc1C#N
C(#N)C=1C=C(C(=O)OC)C=CC1OC(C)C.[OH-].[Na+].FC(C(=O)OC1=C(C(=C(C(=C1F)F)F)F)F)(F)F.C(C)N(CC)CC>>C(#N)C=1C=C(C(=O)OC2=C(C(=C(C(=C2F)F)F)F)F)C=CC1OC(C)C
CO[C:9]([c:8]1[cH:7][cH:6][c:5]([O:4][CH:2]([CH3:1])[CH3:3])[c:24]([C:25]#[N:26])[cH:23]1)=[O:10].O=C(C(F)(F)F)[O:11][c:12]1[c:13]([F:14])[c:15]([F:16])[c:17]([F:18])[c:19]([F:20])[c:21]1[F:22]>>[CH3:1][CH:2]([CH3:3])[O:4][c:5]1[cH:6][cH:7][c:8]([C:9](=[O:10])[O:11][c:12]2[c:13]([F:14])[c:15]([F:16])[c:17]([F:18])[c:19...
COC(=O)c1ccc(OC(C)C)c(C#N)c1.O=C(Oc1c(F)c(F)c(F)c(F)c1F)C(F)(F)F
CC(C)Oc1ccc(C(=O)Oc2c(F)c(F)c(F)c(F)c2F)cc1C#N
null
null
O.CO
Acylation
OtherReaction
580054fc0b51b792707ad4b668033c84495f9aead4f098ebc488ee73871837ea
4458c2810029240f45ce48457089b9a8e19de9f2b2e0fc29ef56ddad657ed962
O=C(Oc1ccccc1)c1ccccc1
C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].F-C(-F)(-F)-C(=O)-[O;H0;D2;+0:6]-[c:7](:[c:8]):[c:9]>>[O;D1;H0:2]=[C;H0;D3;+0:1](-[O;H0;D2;+0:6]-[c:7](:[c:8]):[c:9])-[c:3](:[c:4]):[c:5]
84
[{"value": 83.5, "product": "C(#N)C=1C=C(C(=O)OC2=C(C(=C(C(=C2F)F)F)F)F)C=CC1OC(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 84.0, "product": "C(#N)C=1C=C(C(=O)OC2=C(C(=C(C(=C2F)F)F)F)F)C=CC1OC(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
20.5 g (0.093 mol) of methyl 3-cyano-4-isopropoxybenzoate 4 was dissolved in 200 mL of a 6:4 mixture of methanol and water. To this was added 5.61 g (0.14 mol) of NaOH and the mixture stirred for 2 hours at room temperature. The solution was then filtered through a silica gel plug and the solvents removed under vacuum....
10.6084/m9.figshare.5104873.v1
null
Trifluoro group.Ester.Ester
Ester
null
null
c1ccccc1.c1ccccc1
HF
O.CO
null
2
COC(=O)c1ccc(OC(C)C)c(C#N)c1.O=C(Oc1c(F)c(F)c(F)c(F)c1F)C(F)(F)F>O.CO>CC(C)Oc1ccc(C(=O)Oc2c(F)c(F)c(F)c(F)c2F)cc1C#N
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-0c1da52e41474b6697b13198665d08cb
CC(C)I.CON(C)C(=O)c1nc(-c2ccc(C[C@@H](CCC(=O)OC(C)(C)C)NC(=O)OC(C)(C)C)cc2)cn1C>>COC(=O)c1ccc(O)c(I)c1
CC(C)(C)OC(=O)N[C@H](CCC(=O)OC(C)(C)C)CC1=CC=C(C=C1)C=1N=C(N(C1)C)C(=O)N(OC)C.IC(C)C.CCN(C(C)C)C(C)C.CN(C)C=O>>OC1=C(C=C(C(=O)OC)C=C1)I
C[CH:10]([I:11])[CH3:12].CN([O:2][CH3:1])[C:3](=[O:4])[c:5]1nc(-[c:8]2ccc(C[C@@H](CCC(OC(C)(C)C)=[O:9])NC(=O)OC(C)(C)C)[cH:6][cH:7]2)cn1C>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([OH:9])[c:10]([I:11])[cH:12]1
CC(C)I.CON(C)C(=O)c1nc(-c2ccc(C[C@@H](CCC(=O)OC(C)(C)C)NC(=O)OC(C)(C)C)cc2)cn1C
COC(=O)c1ccc(O)c(I)c1
null
null
null
Acylation
OtherReaction
bdc1f46afe698d9edd26392dbcd953815f1ab48bc01fe39842adc4a9d53bec2e
2908d920a73258e3597d947094497249f48b631e1ac541ab8d68b33e393d3f9b
c1ccccc1
C-N(-[O;H0;D2;+0:1]-[C;D1;H3:2])-[C;H0;D3;+0:3](=[O;D1;H0:4])-[c;H0;D3;+0:5]1:n:c(-[c;H0;D3;+0:6]2:[c:7]:[cH;D2;+0:8]:c(-C-[C@@H](-C-C-C(=[O;H0;D1;+0:9])-O-C(-C)(-C)-C)-N-C(=O)-O-C(-C)(-C)-C):c:c:2):c:n:1-C.C-[CH;D3;+0:10](-[CH3;D1;+0:11])-[I;D1;H0:12]>>[C;D1;H3:2]-[O;H0;D2;+0:1]-[C;H0;D3;+0:3](=[O;D1;H0:4])-[c;H0;D3;+...
20
[{"value": 20.0, "product": "OC1=C(C=C(C(=O)OC)C=C1)I", "details": "PERCENTYIELD", "is_desired": false}]
80
CELSIUS
8
HOUR
To a solution of compound 1 (200 mg, 1.077 mmol) and 2-iodopropane (322 uL, 3.23 mmol) in DMF (10 mL) was added DIEA (750 uL, 4.31 mmol). The reaction mixture was heated to 80° C. and stirred overnight. When complete by LC/MS, the reaction was cooled to room temperature, quenched with HCl (0.5 N, 30 mL) and extracted w...
10.6084/m9.figshare.5104873.v1
null
Secondary halide.Carbamic ester.Ester.Ether.Tertiary amide.Boc.Boc
Aromatic halide.Ester.Aromatic alcohol
c1ncc[nH]1.c1ccccc1
c1ccccc1
c1ccccc1
HO-
null
80
8
CC(C)I.CON(C)C(=O)c1nc(-c2ccc(C[C@@H](CCC(=O)OC(C)(C)C)NC(=O)OC(C)(C)C)cc2)cn1C>>COC(=O)c1ccc(O)c(I)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-920b5700f55d4c98978c714fdc49dafd
COC(=O)c1ccc(O)c(C#N)c1.O=C1CCC(=O)N1Cl>>COC(=O)c1ccc(OC(C)C)c(C#N)c1
C(#N)C=1C=C(C(=O)OC)C=CC1O.ClN1C(CCC1=O)=O>>C(#N)C=1C=C(C(=O)OC)C=CC1OC(C)C
[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([OH:9])[c:13]([C:14]#[N:15])[cH:16]1.O=[C:10]1N(Cl)[C:11](=O)C[CH2:12]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([O:9][CH:10]([CH3:11])[CH3:12])[c:13]([C:14]#[N:15])[cH:16]1
COC(=O)c1ccc(O)c(C#N)c1.O=C1CCC(=O)N1Cl
COC(=O)c1ccc(OC(C)C)c(C#N)c1
null
null
C(C)#N
Heteroatom Alkylation and Arylation
OtherReaction
583eebb8475c3e0259acdbe4597e93f53d9f697a23b264ed51b6dda3df53c69f
05bc6928a21991bad9931d6f39f8fcb40a9f20a9e409334ab947e3e3fa1c19df
c1ccccc1
Cl-N1-[C;H0;D3;+0:1](=O)-[CH2;D2;+0:2]-C-[C;H0;D3;+0:3]-1=O.[OH;D1;+0:4]-[c:5](:[c:6]):[c:7]>>[CH3;D1;+0:3]-[CH;D3;+0:1](-[CH3;D1;+0:2])-[O;H0;D2;+0:4]-[c:5](:[c:6]):[c:7]
80.2
[{"value": 29.0, "product": "C(#N)C=1C=C(C(=O)OC)C=CC1OC(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 80.2, "product": "C(#N)C=1C=C(C(=O)OC)C=CC1OC(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
65
CELSIUS
8
HOUR
A portion of residue 3 (4.19 g, ˜7.45 mmol) was dissolved in acetonitrile (50 mL) and treated with N-chlorosuccinimide (1.19 g, 8.94 mmol) at room temperature. The temperature was raised to 65° C. and the mixture stirred overnight. When LC/MS showed complete conversion of starting material, the mixture was cooled to ro...
10.6084/m9.figshare.5104873.v1
null
Tertiary amide.Tertiary amide.Aromatic alcohol
Ether
C1CCNC1
null
c1ccccc1
Other
C(C)#N
65
8
COC(=O)c1ccc(O)c(C#N)c1.O=C1CCC(=O)N1Cl>C(C)#N>COC(=O)c1ccc(OC(C)C)c(C#N)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-9e0a544a12ff4aa98f2559e51de7b16d
COC(=O)c1ccc(O)c(I)c1>>COC(=O)c1ccc(O)c(C#N)c1
OC1=C(C=C(C(=O)OC)C=C1)I.[H-].[Na+].CN(C)C=O>>C(#N)C=1C=C(C(=O)OC)C=CC1O
I[c:10]1[c:8]([OH:9])[cH:7][cH:6][c:5]([C:3]([O:2][CH3:1])=[O:4])[cH:13]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([OH:9])[c:10]([C:11]#[N:12])[cH:13]1
COC(=O)c1ccc(O)c(I)c1
COC(=O)c1ccc(O)c(C#N)c1
null
null
null
Miscellaneous
OtherReaction
3ae4da8b7f110de99cf8afc091b6f0c8540050148e425770f8030bce1480042c
73a96fe5e833259ca394a42f82d6cc2ee7231bcde92d95030d2893b90c3fef76
c1ccccc1
I-[c;H0;D3;+0:1](:[c:2]:[c:3]-[C:4](-[#8:5])=[O;D1;H0:6]):[c:7](-[O;D1;H1:8]):[c:9]>>[#8:5]-[C:4](=[O;D1;H0:6])-[c:3]:[c:2]:[c;H0;D3;+0:1](-[C:10]#[N;D1;H0:11]):[c:7](-[O;D1;H1:8]):[c:9]
null
[]
null
null
16
HOUR
A solution of compound 2 (6.46 g, 24.1 mmol) in DMF (30 mL) was treated with sodium hydride (1.94 g of 60% dispersion in mineral oil, 48.6 mmol) portionwise at room temperature. The resulting mixture was stirred at room temperature for 16 hours and then partitioned between water (100 mL) and EtOAc (350 mL). The layers ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
Nitrile
c1ccccc1
c1ccccc1
c1ccccc1
I-
null
null
16
COC(=O)c1ccc(O)c(I)c1>>COC(=O)c1ccc(O)c(C#N)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-0e8a3d54af1542a99d90dff7cc6f10d0
COC(=O)c1ccc(O)c(C#N)c1.C[CH2][Zn][CH2]C>>COC(=O)c1ccc(OC(C)C)c(C#N)c1
[NH4+].[Cl-].C(#N)C=1C=C(C(=O)OC)C=CC1O.ClCI.[NH4+].[OH-].C(C)[Zn]CC>>C(#N)C=1C=C(C(=O)OC)C=CC1OC(C)C
[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([OH:9])[c:13]([C:14]#[N:15])[cH:16]1.[CH2]([Zn][CH2][CH3:12])[CH3:11]>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([O:9][CH:10]([CH3:11])[CH3:12])[c:13]([C:14]#[N:15])[cH:16]1
COC(=O)c1ccc(O)c(C#N)c1.C[CH2][Zn][CH2]C
COC(=O)c1ccc(OC(C)C)c(C#N)c1
null
null
ClCCCl.CCOC(=O)C
Heteroatom Alkylation and Arylation
OtherReaction
b8b041187bac58376aae824630608e7deb49a01db3d652291f8b379c10d4e434
0f0966e3597a58033417ecee71659f4d0c082f95d46b1e52c95541e6e4a59086
c1ccccc1
[CH3;D1;+0:1]-[CH2]-[Zn]-[CH2]-[CH3;D1;+0:2].[OH;D1;+0:3]-[c:4](:[c:5]):[c:6]>>[CH3;D1;+0:1]-[C:7](-[CH3;D1;+0:2])-[O;H0;D2;+0:3]-[c:4](:[c:5]):[c:6]
30
[{"value": 30.0, "product": "C(#N)C=1C=C(C(=O)OC)C=CC1OC(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 30.0, "product": "C(#N)C=1C=C(C(=O)OC)C=CC1OC(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
30
MINUTE
Compound 3 (5.56 g, 24.0 mmol) was added to a solution of chloroiodomethane (5.59 mL, 76.8 mmol) in 1,2-dichloroethane (35 mL) under an atmosphere of nitrogen. The solution was cooled to 0° C. with an ice bath and diethyl zinc (38.4 mL, 1.0 M in hexanes, 38.4 mmol) was added over 10 minutes. The resulting mixture was s...
10.6084/m9.figshare.5104873.v1
null
Aromatic alcohol
Ether
null
null
c1ccccc1
Zn
ClCCCl.CCOC(=O)C
0
0.5
COC(=O)c1ccc(O)c(C#N)c1.C[CH2][Zn][CH2]C>ClCCCl.CCOC(=O)C>COC(=O)c1ccc(OC(C)C)c(C#N)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-c1d0828f83814ed690ab3dadd32f6a9f
C[C@@H](NC(=O)CCCCl)c1nc(-c2ccc(I)cc2)cn1C>>C[C@H](c1nc(-c2ccc(I)cc2)cn1C)N1CCCC1=O
CCOC(=O)C.ClCCCC(=O)N[C@H](C)C=1N(C=C(N1)C1=CC=C(C=C1)I)C.C1CCOC1.CC(C)([O-])C.[K+]>>IC1=CC=C(C=C1)C=1N=C(N(C1)C)[C@@H](C)N1C(CCC1)=O
Cl[CH2:17][CH2:18][CH2:19][C:20]([NH:16][C@H:2]([CH3:1])[c:3]1[n:4][c:5](-[c:6]2[cH:7][cH:8][c:9]([I:10])[cH:11][cH:12]2)[cH:13][n:14]1[CH3:15])=[O:21]>>[CH3:1][C@H:2]([c:3]1[n:4][c:5](-[c:6]2[cH:7][cH:8][c:9]([I:10])[cH:11][cH:12]2)[cH:13][n:14]1[CH3:15])[N:16]1[CH2:17][CH2:18][CH2:19][C:20]1=[O:21]
C[C@@H](NC(=O)CCCCl)c1nc(-c2ccc(I)cc2)cn1C
C[C@H](c1nc(-c2ccc(I)cc2)cn1C)N1CCCC1=O
null
null
O
Heteroatom Alkylation and Arylation
OtherReaction
62f43057f012567ee0d9bea97538013537b046013f70e56d5406a05691c3dc0d
4a6c1e88c9e8bed487b746792f88d478ff36cc235f9a217d4632e6babdebdc9a
O=C1CCCN1Cc1nc(-c2ccccc2)c[nH]1
Cl-[CH2;D2;+0:1]-[C:2]-[C:3]-[C:4](=[O;D1;H0:5])-[NH;D2;+0:6]-[C:7](-[C;D1;H3:8])-[c:9](:[#7;a:10]):[#7;a:11]>>[#7;a:10]:[c:9](-[C:7](-[C;D1;H3:8])-[N;H0;D3;+0:6]1-[CH2;D2;+0:1]-[C:2]-[C:3]-[C:4]-1=[O;D1;H0:5]):[#7;a:11]
86
[{"value": 86.0, "product": "IC1=CC=C(C=C1)C=1N=C(N(C1)C)[C@@H](C)N1C(CCC1)=O", "details": "PERCENTYIELD", "is_desired": false}]
0
CELSIUS
1.5
HOUR
To a 20-dram vial was added (R)-4-chloro-N-(1-(4-(4-iodophenyl)-1-methyl-1H-imidazol-2-yl)ethyl)butanamide and THF (10 mL). The vial was cooled to 0° C. under a nitrogen atmosphere and potassium t-butoxide (214 mg, 1.91 mmol) was added. The reaction was stirred for 1.5 h. To the reaction mixture was added EtOAc (50 mL)...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amide
Tertiary amide
null
C1CC[NH]C1
c1cnc[nH]1.c1ccccc1.C1CC[NH]C1
HCl
O
0
1.5
C[C@@H](NC(=O)CCCCl)c1nc(-c2ccc(I)cc2)cn1C>O>C[C@H](c1nc(-c2ccc(I)cc2)cn1C)N1CCCC1=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-8a2a4d712e6a4a46ab05384dc8900b8d
CN[C@H](C)c1nc(-c2ccc(I)cc2)cn1C.COC(=O)Cl>>COC(=O)N(C)[C@H](C)c1nc(-c2ccc(I)cc2)cn1C
IC1=CC=C(C=C1)C=1N=C(N(C1)C)[C@@H](C)NC.ClC(=O)OC.C(=O)([O-])[O-].[Na+].[Na+].C1CCOC1>>IC1=CC=C(C=C1)C=1N=C(N(C1)C)[C@@H](C)N(C(OC)=O)C
[NH:5]([CH3:6])[C@H:7]([CH3:8])[c:9]1[n:10][c:11](-[c:12]2[cH:13][cH:14][c:15]([I:16])[cH:17][cH:18]2)[cH:19][n:20]1[CH3:21].Cl[C:3]([O:2][CH3:1])=[O:4]>>[CH3:1][O:2][C:3](=[O:4])[N:5]([CH3:6])[C@H:7]([CH3:8])[c:9]1[n:10][c:11](-[c:12]2[cH:13][cH:14][c:15]([I:16])[cH:17][cH:18]2)[cH:19][n:20]1[CH3:21]
CN[C@H](C)c1nc(-c2ccc(I)cc2)cn1C.COC(=O)Cl
COC(=O)N(C)[C@H](C)c1nc(-c2ccc(I)cc2)cn1C
null
null
O.CCOC(=O)C
Protection
N-alkylation of secondary amines with alkyl halides
496a200c7c2fc7c000296e03cda40efb8e258ccaeb02fa999285bf74ddc49346
d86dc1e6d0e089b3444b62ddfcf4c4822bdac4b60e628553036562518c29adcd
c1ccc(-c2c[nH]cn2)cc1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#8:3]-[C;D1;H3:4].[#7;a:5]:[c:6](-[C:7](-[C;D1;H3:8])-[NH;D2;+0:9]-[C;D1;H3:10]):[#7;a:11]>>[#7;a:5]:[c:6](-[C:7](-[C;D1;H3:8])-[N;H0;D3;+0:9](-[C;D1;H3:10])-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#8:3]-[C;D1;H3:4]):[#7;a:11]
41.3
[{"value": 41.0, "product": "IC1=CC=C(C=C1)C=1N=C(N(C1)C)[C@@H](C)N(C(OC)=O)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 41.3, "product": "IC1=CC=C(C=C1)C=1N=C(N(C1)C)[C@@H](C)N(C(OC)=O)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
To a 250 mL round bottom flask was added (R)-1-(4-(4-iodophenyl)-1-methyl-1H-imidazol-2-yl)-N-methylethanamine (3.1 g, 9.1 mmol), methyl chloroformate (0.84 mL, 10.9 mmol), Na2CO3 (1.15 g, 10.9 mmol), and THF (100 mL). The reaction was stirred for 2 hours, followed by the addition of EtOAc (50 mL) and water (10 mL). Th...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Ether.Secondary amine
Carbamic ester
null
null
c1cnc[nH]1.c1ccccc1
HCl
O.CCOC(=O)C
null
2
CN[C@H](C)c1nc(-c2ccc(I)cc2)cn1C.COC(=O)Cl>O.CCOC(=O)C>COC(=O)N(C)[C@H](C)c1nc(-c2ccc(I)cc2)cn1C
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-e030e56358fc49f284fb01b326239fb1
CCOC(=O)CBr.COC(=O)c1ccc(O)c(C#N)c1>>COC(=O)c1ccc(OC(C)C)c(C#N)c1
C(#N)C=1C=C(C(=O)OC)C=CC1O.C(=O)([O-])[O-].[K+].[K+].BrCC(=O)OCC>>C(#N)C=1C=C(C(=O)OC)C=CC1OC(C)C
O=[C:10](OC[CH3:12])[CH2:11]Br.[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([OH:9])[c:13]([C:14]#[N:15])[cH:16]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([O:9][CH:10]([CH3:11])[CH3:12])[c:13]([C:14]#[N:15])[cH:16]1
CCOC(=O)CBr.COC(=O)c1ccc(O)c(C#N)c1
COC(=O)c1ccc(OC(C)C)c(C#N)c1
null
null
O.CN(C)C=O
Heteroatom Alkylation and Arylation
OtherReaction
0acf459bf686003717df84cdcc64b7e9112cbac95ec05a938cd5030dbca78e71
f70d7bf1e28f3adbba70880b540f7d6c0ef11f9028ba0dd0b253425838a0a3ab
c1ccccc1
Br-[CH2;D2;+0:1]-[C;H0;D3;+0:2](=O)-O-C-[CH3;D1;+0:3].[OH;D1;+0:4]-[c:5](:[c:6]):[c:7]>>[CH3;D1;+0:1]-[CH;D3;+0:2](-[CH3;D1;+0:3])-[O;H0;D2;+0:4]-[c:5](:[c:6]):[c:7]
189.5
[{"value": 91.0, "product": "C(#N)C=1C=C(C(=O)OC)C=CC1OC(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 189.5, "product": "C(#N)C=1C=C(C(=O)OC)C=CC1OC(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
60
CELSIUS
3
HOUR
To a solution of compound 3 (2.66 g, 7.27 mmol) in DMF (15 mL) was added K2CO3 (2.00 g, 15 mmol) and ethyl bromoacetate (1.61 mL, 14.5 mmol). The resulting mixture was stirred at 60° C. for three hours. The mixture was diluted with water and extracted with EtOAc (3×50 mL). The organic layers were combined, dried over N...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester.Aromatic alcohol
Ether
null
null
c1ccccc1
HBr
O.CN(C)C=O
60
3
CCOC(=O)CBr.COC(=O)c1ccc(O)c(C#N)c1>O.CN(C)C=O>COC(=O)c1ccc(OC(C)C)c(C#N)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-b50a8b6695f44fe6b0f3f331f83d2e58
CC(C)(C)OC(=O)C(N)CBr.COC(=O)c1ccc(O)c(C#N)c1>>COC(=O)c1ccc(OC(C)C)c(C#N)c1
C(#N)C=1C=C(C(=O)OC)C=CC1O.C(=O)([O-])[O-].[K+].[K+].C(=O)(OC(C)(C)C)C(CBr)N>>C(#N)C=1C=C(C(=O)OC)C=CC1OC(C)C
C[C:10](OC(=O)C(N)CBr)([CH3:11])[CH3:12].[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([OH:9])[c:13]([C:14]#[N:15])[cH:16]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([O:9][CH:10]([CH3:11])[CH3:12])[c:13]([C:14]#[N:15])[cH:16]1
CC(C)(C)OC(=O)C(N)CBr.COC(=O)c1ccc(O)c(C#N)c1
COC(=O)c1ccc(OC(C)C)c(C#N)c1
null
null
O.CN(C)C=O
Heteroatom Alkylation and Arylation
OtherReaction
d647953592dc0ff19485d3d76908e40e976b37d36428179cea834c18dbe35c6c
3e561a7fd54c45848554c88ca1b48fe4ef24292d518b5a7f61512c34f16d817e
c1ccccc1
Br-C-C(-N)-C(=O)-O-[C;H0;D4;+0:1](-C)(-[C;D1;H3:2])-[C;D1;H3:3].[OH;D1;+0:4]-[c:5](:[c:6]):[c:7]>>[C;D1;H3:2]-[CH;D3;+0:1](-[C;D1;H3:3])-[O;H0;D2;+0:4]-[c:5](:[c:6]):[c:7]
109.5
[{"value": 55.0, "product": "C(#N)C=1C=C(C(=O)OC)C=CC1OC(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 109.5, "product": "C(#N)C=1C=C(C(=O)OC)C=CC1OC(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
60
CELSIUS
3
HOUR
To a solution of compound 3 (5.000 g, 17 mmol) in DMF (15 mL) was added K2CO3 (3.51 g, 26 mmol) and Boc-2-amino ethyl bromide (4.56 g, 20.35 mmol). The resulting mixture was stirred at 60° C. for three hours. The mixture was diluted with water and extracted with EtOAc (3×50 mL). The organic layers were combined, dried ...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester.Aromatic alcohol.Primary amine.Boc
Ether
null
null
c1ccccc1
HBr
O.CN(C)C=O
60
3
CC(C)(C)OC(=O)C(N)CBr.COC(=O)c1ccc(O)c(C#N)c1>O.CN(C)C=O>COC(=O)c1ccc(OC(C)C)c(C#N)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-1b618945e8ee4a949f3775139fc56571
CN(C)C.COC(=O)c1ccc(O)c(I)c1>>COC(=O)c1ccc(O)c(C#N)c1
CC(C)(C)OC(=O)OC(=O)OC(C)(C)C.OC1=C(C=C(C(=O)OC)C=C1)I.CN(C)C.O1CCOCC1>>C(#N)C=1C=C(C(=O)OC)C=CC1O
C[N:12](C)[CH3:11].I[c:10]1[c:8]([OH:9])[cH:7][cH:6][c:5]([C:3]([O:2][CH3:1])=[O:4])[cH:13]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([OH:9])[c:10]([C:11]#[N:12])[cH:13]1
CN(C)C.COC(=O)c1ccc(O)c(I)c1
COC(=O)c1ccc(O)c(C#N)c1
null
null
O
C-C Coupling
OtherReaction
1a14070cbe6fe5f59309149001ffa2dfc322a156a861405855acfdd6362705a6
951efce9f7401e9a96fe9b4f90874368f054ec53732a86c28b3b95242d371d1a
c1ccccc1
C-[N;H0;D3;+0:1](-C)-[CH3;D1;+0:2].I-[c;H0;D3;+0:3](:[c:4]:[c:5]-[C:6](-[#8:7])=[O;D1;H0:8]):[c:9](-[O;D1;H1:10]):[c:11]>>[#8:7]-[C:6](=[O;D1;H0:8])-[c:5]:[c:4]:[c;H0;D3;+0:3](-[C;H0;D2;+0:2]#[N;H0;D1;+0:1]):[c:9](-[O;D1;H1:10]):[c:11]
154.5
[{"value": 97.0, "product": "C(#N)C=1C=C(C(=O)OC)C=CC1O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 154.5, "product": "C(#N)C=1C=C(C(=O)OC)C=CC1O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
10
MINUTE
(Boc)2O (44.7 g, 0.21 mol) was added portion-wise over 10 min to a 0° C. solution of compound 2 (42 g, 0.19 mol), trimethyl amine (51.9 mL, 0.37 mol), dioxane (140 mL) and water (56 mL). After another 10 min, the ice bath was removed and the reaction mixture was stirred while warming to room temperature for another 2 h...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Tertiary amine
Nitrile
c1ccccc1
c1ccccc1
c1ccccc1
HI
O
null
0.166667
CN(C)C.COC(=O)c1ccc(O)c(I)c1>O>COC(=O)c1ccc(O)c(C#N)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-cfc606fe8ccd4addb3c5045bc889d98b
CCN(C(C)C)C(C)C.COC(=O)c1ccc(O)c(I)c1>>COC(=O)c1ccc(O)c(C#N)c1
OC1=C(C=C(C(=O)OC)C=C1)I.CCN(C(C)C)C(C)C.ClC(=O)OCC1=CC=CC=C1>>C(#N)C=1C=C(C(=O)OC)C=CC1O
CC(C)[N:12](C(C)C)[CH2:11]C.I[c:10]1[c:8]([OH:9])[cH:7][cH:6][c:5]([C:3]([O:2][CH3:1])=[O:4])[cH:13]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([OH:9])[c:10]([C:11]#[N:12])[cH:13]1
CCN(C(C)C)C(C)C.COC(=O)c1ccc(O)c(I)c1
COC(=O)c1ccc(O)c(C#N)c1
null
null
C1CCOC1
C-C Coupling
OtherReaction
1a14070cbe6fe5f59309149001ffa2dfc322a156a861405855acfdd6362705a6
951efce9f7401e9a96fe9b4f90874368f054ec53732a86c28b3b95242d371d1a
c1ccccc1
C-[CH2;D2;+0:1]-[N;H0;D3;+0:2](-C(-C)-C)-C(-C)-C.I-[c;H0;D3;+0:3](:[c:4]:[c:5]-[C:6](-[#8:7])=[O;D1;H0:8]):[c:9](-[O;D1;H1:10]):[c:11]>>[#8:7]-[C:6](=[O;D1;H0:8])-[c:5]:[c:4]:[c;H0;D3;+0:3](-[C;H0;D2;+0:1]#[N;H0;D1;+0:2]):[c:9](-[O;D1;H1:10]):[c:11]
100
[{"value": 100.0, "product": "C(#N)C=1C=C(C(=O)OC)C=CC1O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
To a stirred solution of 2 (0.376 mol), DIEA (196 mL, 1.13 mol) and THF (200 mL) was added benzyl chloroformate (59.0 mL, 0.414 mol) dropwise. After the reaction solution was stirred at room temperature for 1 hr, the solution was concentrated on a rotovap. The residue was partitioned between sat. NaHCO3 (300 mL) and di...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Tertiary amine
Nitrile
c1ccccc1
c1ccccc1
c1ccccc1
HI
C1CCOC1
null
1
CCN(C(C)C)C(C)C.COC(=O)c1ccc(O)c(I)c1>C1CCOC1>COC(=O)c1ccc(O)c(C#N)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-f29e0524d2bb4f16898678943a66f3e1
C1CCOC1.COC(=O)c1ccc(O)c(C#N)c1>>COC(=O)c1ccc(OC(C)C)c(C#N)c1
C(#N)C=1C=C(C(=O)OC)C=CC1O.[OH-].[Li+].C1CCOC1>>C(#N)C=1C=C(C(=O)OC)C=CC1OC(C)C
C1O[CH2:10][CH2:11][CH2:12]1.[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([OH:9])[c:13]([C:14]#[N:15])[cH:16]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([O:9][CH:10]([CH3:11])[CH3:12])[c:13]([C:14]#[N:15])[cH:16]1
C1CCOC1.COC(=O)c1ccc(O)c(C#N)c1
COC(=O)c1ccc(OC(C)C)c(C#N)c1
null
null
O
Heteroatom Alkylation and Arylation
OtherReaction
af6431764d7b6a0c53b29e6ba52c7e7b20102fffae4ff7bf8df31e9993d83889
c914f6fa2d9eafe4b7954ab7b93ff3a695a6ab65e94131aace66d55280701a93
c1ccccc1
C1-O-[CH2;D2;+0:1]-[CH2;D2;+0:2]-[CH2;D2;+0:3]-1.[OH;D1;+0:4]-[c:5](:[c:6]):[c:7]>>[CH3;D1;+0:2]-[CH;D3;+0:1](-[CH3;D1;+0:3])-[O;H0;D2;+0:4]-[c:5](:[c:6]):[c:7]
null
[]
null
null
2
HOUR
To a solution of 3 (0.376 mol) in THF (200 mL) and water (100 mL) was added lithium hydroxide (31.6 g, 0.752 mol) and the mixture stirred for 2 hours. The reaction mixture was filtered through a silica gel plug (the pH of the filtrate was about 7) and concentrated. The residue was dried under vacuum to give 4 (0.376 mo...
10.6084/m9.figshare.5104873.v1
null
Ether.Aromatic alcohol
Ether
C1CCOC1
null
c1ccccc1
HO-
O
null
2
C1CCOC1.COC(=O)c1ccc(O)c(C#N)c1>O>COC(=O)c1ccc(OC(C)C)c(C#N)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-f16339f8d9b1499c868c368060cf71af
CNOC.COC(=O)c1ccc(O)c(I)c1>>COC(=O)c1ccc(O)c(C#N)c1
OC1=C(C=C(C(=O)OC)C=C1)I.CN(C)C(=[N+](C)C)ON1C2=C(C=CC=C2)N=N1.F[P-](F)(F)(F)(F)F.C=1C=CC2=C(C1)N=NN2O.Cl.CNOC.CCN(C(C)C)C(C)C>>C(#N)C=1C=C(C(=O)OC)C=CC1O
CO[NH:12][CH3:11].I[c:10]1[c:8]([OH:9])[cH:7][cH:6][c:5]([C:3]([O:2][CH3:1])=[O:4])[cH:13]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([OH:9])[c:10]([C:11]#[N:12])[cH:13]1
CNOC.COC(=O)c1ccc(O)c(I)c1
COC(=O)c1ccc(O)c(C#N)c1
null
null
CN(C)C=O
C-C Coupling
OtherReaction
0ddd49a1ca8b111466f27ea4250bfb9e859aa35592534618400427517f0d77d6
0f2f52485e0ef8d6cbb70f9be8e5a149bfe9ccf0be105523f3e66890b5410df9
c1ccccc1
C-O-[NH;D2;+0:1]-[CH3;D1;+0:2].I-[c;H0;D3;+0:3](:[c:4]:[c:5]-[C:6](-[#8:7])=[O;D1;H0:8]):[c:9](-[O;D1;H1:10]):[c:11]>>[#8:7]-[C:6](=[O;D1;H0:8])-[c:5]:[c:4]:[c;H0;D3;+0:3](-[C;H0;D2;+0:2]#[N;H0;D1;+0:1]):[c:9](-[O;D1;H1:10]):[c:11]
295.8
[{"value": 78.0, "product": "C(#N)C=1C=C(C(=O)OC)C=CC1O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 295.8, "product": "C(#N)C=1C=C(C(=O)OC)C=CC1O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
To a solution of 2 (1.49 g, 2.29 mmol), HBTU (1.3 g, 3.44 mmol), HOBt (530 mg, 3.44 mmol), and N,O-dimethylhydroxylamine HCl salt (340 mg, 3.44 mmol) in DMF (20 mL) was added DIEA (785 uL, 4.58 mmol). The resulting mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated. The resulting...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Nitrile
c1ccccc1
c1ccccc1
c1ccccc1
HI
CN(C)C=O
null
2
CNOC.COC(=O)c1ccc(O)c(I)c1>CN(C)C=O>COC(=O)c1ccc(O)c(C#N)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-bc0cd75241084bb68e017a12ce2302cb
CC(C)(C)[Si](C)(C)OCCBr.COC(=O)c1ccc(O)c(C#N)c1>>COC(=O)c1ccc(OC(C)C)c(C#N)c1
[H-].[Na+].C(#N)C=1C=C(C(=O)OC)C=CC1O.BrCCO[Si](C)(C)C(C)(C)C>>C(#N)C=1C=C(C(=O)OC)C=CC1OC(C)C
C[Si](C)(OCCBr)[C:10](C)([CH3:11])[CH3:12].[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([OH:9])[c:13]([C:14]#[N:15])[cH:16]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([O:9][CH:10]([CH3:11])[CH3:12])[c:13]([C:14]#[N:15])[cH:16]1
CC(C)(C)[Si](C)(C)OCCBr.COC(=O)c1ccc(O)c(C#N)c1
COC(=O)c1ccc(OC(C)C)c(C#N)c1
null
null
CN(C)C=O.CCOC(=O)C
Heteroatom Alkylation and Arylation
OtherReaction
7f22a03d1c7e423e260723257a54d81f1d7cd177ee2db6ae056344e211816325
e5e494b410b54158ffcc29f62b8b911f348201ee0ca0a61b5b612710c1345ff8
c1ccccc1
Br-C-C-O-[Si](-C)(-C)-[C;H0;D4;+0:1](-C)(-[C;D1;H3:2])-[C;D1;H3:3].[OH;D1;+0:4]-[c:5](:[c:6]):[c:7]>>[C;D1;H3:2]-[CH;D3;+0:1](-[C;D1;H3:3])-[O;H0;D2;+0:4]-[c:5](:[c:6]):[c:7]
84.2
[{"value": 41.0, "product": "C(#N)C=1C=C(C(=O)OC)C=CC1OC(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 84.2, "product": "C(#N)C=1C=C(C(=O)OC)C=CC1OC(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1.5
HOUR
To a suspension of NaH (0.39 g, 9.3 mmol) in DMF (15 mL) was added a solution of 3 (1.9 g, 6.5 mmol) in DMF (10 mL) at 0° C. under nitrogen. The reaction was stirred for 1.5 h, and then (2-bromoethoxy)-tert-butyldimethylsilane (2.09 mL, 9.7 mmol) was added. The reaction mixture was stirred overnight, diluted with EtOAc...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol.TMS ether protective group
Ether
null
null
c1ccccc1
HBr
CN(C)C=O.CCOC(=O)C
null
1.5
CC(C)(C)[Si](C)(C)OCCBr.COC(=O)c1ccc(O)c(C#N)c1>CN(C)C=O.CCOC(=O)C>COC(=O)c1ccc(OC(C)C)c(C#N)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ac7799ce05b84b0c934960ba95b9a2f2
CO.COC(=O)c1ccc(O)c(C#N)c1>>COC(=O)c1ccc(OC(C)C)c(C#N)c1
C(#N)C=1C=C(C(=O)OC)C=CC1O.[BH4-].[Na+].C1CCOC1.CO>>C(#N)C=1C=C(C(=O)OC)C=CC1OC(C)C
O[CH3:12].[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([OH:9])[c:13]([C:14]#[N:15])[cH:16]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([O:9][CH:10]([CH3:11])[CH3:12])[c:13]([C:14]#[N:15])[cH:16]1
CO.COC(=O)c1ccc(O)c(C#N)c1
COC(=O)c1ccc(OC(C)C)c(C#N)c1
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
4622e7934dd5328af1014056d8882932e5f303d08f873e671539ebf0ad57f848
51e77d0fe280879eec2f84298441067b61501ac5af19ab94008f56517f7456b2
c1ccccc1
O-[CH3;D1;+0:1].[OH;D1;+0:2]-[c:3](:[c:4]):[c:5]>>[C;D1;H3:6]-[C:7](-[CH3;D1;+0:1])-[O;H0;D2;+0:2]-[c:3](:[c:4]):[c:5]
99
[{"value": 99.0, "product": "C(#N)C=1C=C(C(=O)OC)C=CC1OC(C)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
10
MINUTE
To a solution of 3 (3.0 g, 10.8 mmol) in THF/MeOH (10 mL/10 mL) was slowly added NaBH4 (407 mg, 10.8 mmol). The mixture was stirred for 10 min, quenched by saturated NH4Cl and partitioned between EtOAc and H2O. The organic layer was washed with sat NaHCO3 and brine, dried over Na2SO4, filtered and concentrated to give ...
10.6084/m9.figshare.5104873.v1
null
Aromatic alcohol.Methanol
Ether
null
null
c1ccccc1
null
null
null
0.166667
CO.COC(=O)c1ccc(O)c(C#N)c1>>COC(=O)c1ccc(OC(C)C)c(C#N)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-8ca2049a89034a2283d41632e74ea623
CN.COC(=O)c1ccc(O)c(I)c1>>COC(=O)c1ccc(O)c(C#N)c1
CN.CN(C)C(=[N+](C)C)ON1C2=C(C=CC=C2)N=N1.F[P-](F)(F)(F)(F)F.CN(C)C=O.OC1=C(C=C(C(=O)OC)C=C1)I.CCN(C(C)C)C(C)C>>C(#N)C=1C=C(C(=O)OC)C=CC1O
[CH3:11][NH2:12].I[c:10]1[c:8]([OH:9])[cH:7][cH:6][c:5]([C:3]([O:2][CH3:1])=[O:4])[cH:13]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([OH:9])[c:10]([C:11]#[N:12])[cH:13]1
CN.COC(=O)c1ccc(O)c(I)c1
COC(=O)c1ccc(O)c(C#N)c1
null
null
null
C-C Coupling
OtherReaction
72645260c477d5d59b8c28a3f4573e1873a19c2dd5bbf1a5cee92a7bb55ad2bd
331eba5143cc034fe99c4177c9125849def30dd58d39bbddf9a53d024fc826ff
c1ccccc1
I-[c;H0;D3;+0:1](:[c:2]:[c:3]-[C:4](-[#8:5])=[O;D1;H0:6]):[c:7](-[O;D1;H1:8]):[c:9].[CH3;D1;+0:10]-[NH2;D1;+0:11]>>[#8:5]-[C:4](=[O;D1;H0:6])-[c:3]:[c:2]:[c;H0;D3;+0:1](-[C;H0;D2;+0:10]#[N;H0;D1;+0:11]):[c:7](-[O;D1;H1:8]):[c:9]
144.6
[{"value": 63.0, "product": "C(#N)C=1C=C(C(=O)OC)C=CC1O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 144.6, "product": "C(#N)C=1C=C(C(=O)OC)C=CC1O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
14
HOUR
To a solution of 11n DMF (158 mg, 0.41 mmol) were added amino acid 2 (100 mg, 0.52 mmol) and DIEA (272 μL, 0.16 mmol). The reaction was stirred for 14 h. Methylamine (2 M in THF, 0.4 mL) and HBTU (295 mg, 0.78 mmol) were then added. The reaction mixture was stirred for 5 h. The product was purified by RP-HPLC using a m...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Nitrile
c1ccccc1
c1ccccc1
c1ccccc1
HI
null
null
14
CN.COC(=O)c1ccc(O)c(I)c1>>COC(=O)c1ccc(O)c(C#N)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-0a30d3f277fd4fedbbdb5f96906d6dfe
CC(C)Oc1ccc(C(=O)O)cc1Cl.CO>>COC(=O)c1ccc(OC(C)C)c(Cl)c1
ClC=1C=C(C(=O)O)C=CC1OC(C)C.O=S(Cl)Cl.CO>>ClC=1C=C(C(=O)OC)C=CC1OC(C)C
O[C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([O:9][CH:10]([CH3:11])[CH3:12])[c:13]([Cl:14])[cH:15]1.[CH3:1][OH:2]>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([O:9][CH:10]([CH3:11])[CH3:12])[c:13]([Cl:14])[cH:15]1
CC(C)Oc1ccc(C(=O)O)cc1Cl.CO
COC(=O)c1ccc(OC(C)C)c(Cl)c1
null
null
null
Protection
Esterification of Carboxylic Acids
9cecdbd189c6f9c3648521d17154d013842a5498de4e76e65efb1d842973340b
af0b8064f2e82ebe66c4c29d2391785ac1b993104265ccdc4d67ca79e36fa3c8
c1ccccc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C;D1;H3:6]-[OH;D1;+0:7]>>[C;D1;H3:6]-[O;H0;D2;+0:7]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
null
[]
null
null
8
HOUR
A solution of 3-chloro-4-[(1-methylethyl)oxy]benzoic acid (1.00 g, 4.66 mmol) in methanol (10.0 mL) was treated with SOCl2 (0.68 mL, 9.32 mmol). After stirring overnight at ambient temperature, the solution was concentrated in vacuo and taken on without purification. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.04 (d, J=2.3 ...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Methanol
Ester
null
null
c1ccccc1
HO-
null
null
8
CC(C)Oc1ccc(C(=O)O)cc1Cl.CO>>COC(=O)c1ccc(OC(C)C)c(Cl)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ae51bcc327cb458ea8bb426605580193
COc1cc(CO)ccc1OCc1ccccc1.CS(=O)(=O)Cl>>COc1cc(COS(C)(=O)=O)ccc1OCc1ccccc1
COC=1C=C(CO)C=CC1OCC1=CC=CC=C1.CS(=O)(=O)Cl.CCN(CC)CC>>CS(=O)(=O)OCC1=CC(=C(C=C1)OCC1=CC=CC=C1)OC
[CH3:1][O:2][c:3]1[cH:4][c:5]([CH2:6][OH:7])[cH:12][cH:13][c:14]1[O:15][CH2:16][c:17]1[cH:18][cH:19][cH:20][cH:21][cH:22]1.Cl[S:8]([CH3:9])(=[O:10])=[O:11]>>[CH3:1][O:2][c:3]1[cH:4][c:5]([CH2:6][O:7][S:8]([CH3:9])(=[O:10])=[O:11])[cH:12][cH:13][c:14]1[O:15][CH2:16][c:17]1[cH:18][cH:19][cH:20][cH:21][cH:22]1
COc1cc(CO)ccc1OCc1ccccc1.CS(=O)(=O)Cl
COc1cc(COS(C)(=O)=O)ccc1OCc1ccccc1
null
null
C(Cl)Cl
Acylation
Formation of Sulfonic Esters
2fa969eb2c954bb96793348a1b2335ec63fbd290dadec6e3e02295e1768e64cf
cb77b899e4adf980b1def97230ef2861660fd7f9602260ec64747d9afd3a795a
c1ccc(COc2ccccc2)cc1
Cl-[S;H0;D4;+0:1](-[C;D1;H3:2])(=[O;D1;H0:3])=[O;D1;H0:4].[OH;D1;+0:5]-[C:6]-[c:7]>>[C;D1;H3:2]-[S;H0;D4;+0:1](=[O;D1;H0:3])(=[O;D1;H0:4])-[O;H0;D2;+0:5]-[C:6]-[c:7]
null
[]
null
null
1
HOUR
A solution of 3-(methoxy)-4-(benzyloxy)benzyl alcohol (0.244 g, 1.00 mmol) in CH2Cl2 (2.0 mL) was treated with methanesulfonylchloride (0.085 mL, 1.10 mmol) and Et3N (0.160 mL, 1.15 mmol). After stirring 1 h at ambient temperature, the reaction mixture was filtered through a short plug of silica gel using CH2Cl2 as the...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Sulfonyl halide
Mesylate
null
null
c1ccccc1.c1ccccc1
HCl
C(Cl)Cl
null
1
COc1cc(CO)ccc1OCc1ccccc1.CS(=O)(=O)Cl>C(Cl)Cl>COc1cc(COS(C)(=O)=O)ccc1OCc1ccccc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-552fe5579ef244128c921a2d04d6d12b
COC(=O)c1ccc(N)c(N)c1.O=Cc1ccccc1>>COC(=O)c1ccc2[nH]c(-c3ccccc3)nc2c1
O.NC=1C=C(C(=O)OC)C=CC1N.OS(=O)[O-].[Na+].C(C1=CC=CC=C1)=O>>C1(=CC=CC=C1)C1=NC2=C(N1)C=CC(=C2)C(=O)OC
[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([NH2:9])[c:18]([NH2:17])[cH:19]1.O=[CH:10][c:11]1[cH:12][cH:13][cH:14][cH:15][cH:16]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]2[nH:9][c:10](-[c:11]3[cH:12][cH:13][cH:14][cH:15][cH:16]3)[n:17][c:18]2[cH:19]1
COC(=O)c1ccc(N)c(N)c1.O=Cc1ccccc1
COC(=O)c1ccc2[nH]c(-c3ccccc3)nc2c1
null
null
C(C)O
Aromatic Heterocycle Formation
Benzimidazole aldehyde
357211f0cea48f6066cc617c063d8f639b186739754abf69a9bef955d42b7d06
947e8e758a50553bad3d8f39fd1540e5051c4c73055f7a5a9da00894523e8ba0
c1ccc(-c2nc3ccccc3[nH]2)cc1
O=[CH;D2;+0:1]-[c;H0;D3;+0:2](:[c:3]:[c:4]):[c:5]:[c:6].[NH2;D1;+0:7]-[c:8](:[c:9]):[c:10](-[NH2;D1;+0:11]):[c:12]>>[c:4]:[c:3]:[c;H0;D3;+0:2](-[c;H0;D3;+0:1]1:[n;H0;D2;+0:7]:[c:8](:[c:9]):[c:10](:[c:12]):[nH;D2;+0:11]:1):[c:5]:[c:6]
97.1
[{"value": 97.0, "product": "C1(=CC=CC=C1)C1=NC2=C(N1)C=CC(=C2)C(=O)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 97.1, "product": "C1(=CC=CC=C1)C1=NC2=C(N1)C=CC(=C2)C(=O)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
An aqueous solution of NaHSO3 (21.0 mL, 40% in water) was treated benzaldehyde (2.00 mL, 20.0 mmol) and stirred at ambient temperature for 1 h. A solution of methyl 3,4-diaminobenzoate (3.32 g, 20.0 mmol) in ethanol (15.0 mL) was added and the solution was heated to reflux for 6 h. Upon cooling, the solution was poured...
10.6084/m9.figshare.5104873.v1
null
Aldehyde.Primary amine.Primary amine
null
c1ccccc1
c1ccc2[nH]cnc2c1
c1ccc2[nH]cnc2c1.c1ccccc1
HO-
C(C)O
null
1
COC(=O)c1ccc(N)c(N)c1.O=Cc1ccccc1>C(C)O>COC(=O)c1ccc2[nH]c(-c3ccccc3)nc2c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-4e31a158b2454566ac7ae5cdb4d06eaf
COC(=O)c1ccc(C=O)cc1.Nc1ccccc1N>>COC(=O)c1ccc(-c2nc3ccccc3[nH]2)cc1
OS(=O)[O-].[Na+].C(=O)C1=CC=C(C(=O)OC)C=C1.C=1(C(=CC=CC1)N)N>>N1C(=NC2=C1C=CC=C2)C2=CC=C(C(=O)OC)C=C2
O=[CH:9][c:8]1[cH:7][cH:6][c:5]([C:3]([O:2][CH3:1])=[O:4])[cH:19][cH:18]1.[NH2:10][c:11]1[cH:12][cH:13][cH:14][cH:15][c:16]1[NH2:17]>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8](-[c:9]2[n:10][c:11]3[cH:12][cH:13][cH:14][cH:15][c:16]3[nH:17]2)[cH:18][cH:19]1
COC(=O)c1ccc(C=O)cc1.Nc1ccccc1N
COC(=O)c1ccc(-c2nc3ccccc3[nH]2)cc1
null
null
C(C)O
Aromatic Heterocycle Formation
Benzimidazole aldehyde
357211f0cea48f6066cc617c063d8f639b186739754abf69a9bef955d42b7d06
947e8e758a50553bad3d8f39fd1540e5051c4c73055f7a5a9da00894523e8ba0
c1ccc(-c2nc3ccccc3[nH]2)cc1
O=[CH;D2;+0:1]-[c;H0;D3;+0:2](:[c:3]:[c:4]):[c:5]:[c:6].[NH2;D1;+0:7]-[c:8](:[c:9]):[c:10](-[NH2;D1;+0:11]):[c:12]>>[c:9]:[c:8]1:[n;H0;D2;+0:7]:[c;H0;D3;+0:1](-[c;H0;D3;+0:2](:[c:3]:[c:4]):[c:5]:[c:6]):[nH;D2;+0:11]:[c:10]:1:[c:12]
100.6
[{"value": 100.0, "product": "N1C(=NC2=C1C=CC=C2)C2=CC=C(C(=O)OC)C=C2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 100.6, "product": "N1C(=NC2=C1C=CC=C2)C2=CC=C(C(=O)OC)C=C2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
An aqueous solution of NaHSO3 (20.0 mL, 40% in water) was treated with a solution of methyl 4-formylbenzoate (2.20 g, 13.4 mmol) in ethanol (15.0 mL) and stirred at ambient temperature for 1 h. 1,2-benzenediamine (1.45 g, 13.4 mmol) was added and the solution was heated to reflux overnight. Upon cooling, the solution w...
10.6084/m9.figshare.5104873.v1
null
Aldehyde.Primary amine.Primary amine
null
c1ccccc1
c1ccc2[nH]cnc2c1
c1ccccc1.c1ccc2[nH]cnc2c1
HO-
C(C)O
null
1
COC(=O)c1ccc(C=O)cc1.Nc1ccccc1N>C(C)O>COC(=O)c1ccc(-c2nc3ccccc3[nH]2)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ab9c3cf2391943e49c30e3416d793f1f
CC(C)(C)C(=N)N.O=C(CBr)c1ccc(Br)cc1>>CC(C)(C)c1nc(-c2ccc(Br)cc2)c[nH]1
BrCC(=O)C1=CC=C(C=C1)Br.CC(C)(C)C(=N)N.Cl.C(=O)([O-])[O-].[K+].[K+]>>BrC1=CC=C(C=C1)C=1N=C(NC1)C(C)(C)C
[CH3:1][C:2]([CH3:3])([CH3:4])[C:5](=[NH:6])[NH2:16].O=[C:7]([c:8]1[cH:9][cH:10][c:11]([Br:12])[cH:13][cH:14]1)[CH2:15]Br>>[CH3:1][C:2]([CH3:3])([CH3:4])[c:5]1[n:6][c:7](-[c:8]2[cH:9][cH:10][c:11]([Br:12])[cH:13][cH:14]2)[cH:15][nH:16]1
CC(C)(C)C(=N)N.O=C(CBr)c1ccc(Br)cc1
CC(C)(C)c1nc(-c2ccc(Br)cc2)c[nH]1
null
null
CN(C=O)C
Aromatic Heterocycle Formation
OtherReaction
d2a4eb5efb5d3f8ece8990722bf83ca46747550c01c6b5b8655072b32188db66
9e77d52183fdbe84f0d2ab96039aaf521caea9340e743bdc6436175f1a3bbdb6
c1ccc(-c2c[nH]cn2)cc1
Br-[CH2;D2;+0:1]-[C;H0;D3;+0:2](=O)-[c;H0;D3;+0:3](:[c:4]:[c:5]):[c:6]:[c:7].[C;D1;H3:8]-[C:9](-[C;D1;H3:10])(-[C;D1;H3:11])-[C;H0;D3;+0:12](-[NH2;D1;+0:13])=[NH;D1;+0:14]>>[C;D1;H3:8]-[C:9](-[C;D1;H3:10])(-[C;D1;H3:11])-[c;H0;D3;+0:12]1:[n;H0;D2;+0:14]:[c;H0;D3;+0:2](-[c;H0;D3;+0:3](:[c:4]:[c:5]):[c:6]:[c:7]):[cH;D2;+...
81
[{"value": 81.0, "product": "BrC1=CC=C(C=C1)C=1N=C(NC1)C(C)(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 80.7, "product": "BrC1=CC=C(C=C1)C=1N=C(NC1)C(C)(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
50
CELSIUS
null
null
A solution of 2,4′-dibromoacetophenone (4.17 g, 15.0 mmol) in N,N-dimethylformamide (60.0 mL) was treated with t-butylcarbamidine hydrochloride (2.05 g, 15.0 mmol) and K2CO3 (4.15 g, 30.0 mmol) and heated to 50° C. for 4 h. Following cooling, the reaction was quenched with water, diluted with brine, and extracted thric...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ketone.Primary amine
null
null
c1c[nH]cn1
c1c[nH]cn1.c1ccccc1
HBr
CN(C=O)C
50
null
CC(C)(C)C(=N)N.O=C(CBr)c1ccc(Br)cc1>CN(C=O)C>CC(C)(C)c1nc(-c2ccc(Br)cc2)c[nH]1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-645cad6ba0e440379f971cb754f59817
CC(C)Oc1ccc(C(=O)O)cc1C#N.NN>>CC(C)Oc1ccc(C(=O)NN)cc1C#N
O.NN.C(#N)C=1C=C(C(=O)O)C=CC1OC(C)C.C(=O)(N1C=NC=C1)N1C=NC=C1>>C(#N)C=1C=C(C(=O)NN)C=CC1OC(C)C
O[C:9]([c:8]1[cH:7][cH:6][c:5]([O:4][CH:2]([CH3:1])[CH3:3])[c:14]([C:15]#[N:16])[cH:13]1)=[O:10].[NH2:11][NH2:12]>>[CH3:1][CH:2]([CH3:3])[O:4][c:5]1[cH:6][cH:7][c:8]([C:9](=[O:10])[NH:11][NH2:12])[cH:13][c:14]1[C:15]#[N:16]
CC(C)Oc1ccc(C(=O)O)cc1C#N.NN
CC(C)Oc1ccc(C(=O)NN)cc1C#N
null
null
O1CCCC1
Acylation
Carboxylic acid with primary amine to amide
87776deec7c8d787307af11af64c4c1226af5b5e46e4fe8124762f384e2eebf3
82203b4f77b2f7d17908f28dcc1ecc7f616d152f963b273ffea1254f61a0fe2d
c1ccccc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[N;D1;H2:6]-[NH2;D1;+0:7]>>[N;D1;H2:6]-[NH;D2;+0:7]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
95
[{"value": 95.0, "product": "C(#N)C=1C=C(C(=O)NN)C=CC1OC(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 95.0, "product": "C(#N)C=1C=C(C(=O)NN)C=CC1OC(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
A solution of 3-cyano-4-[(1-methylethyl)oxy]benzoic acid (0.300 g, 1.46 mmol) in tetrahydrofuran (10.0 mL) was treated with 1,1′-carbonyldiimidazole (0.261 g, 1.61 mmol). After stirring 2 h at ambient temperature, hydrazine monohydrate (0.213 mL, 4.39 mmol) was added. After stirring an additional 2 h at ambient tempera...
10.6084/m9.figshare.5104873.v1
null
Hydrazine.Carboxylic acid
Acylhydrazine
null
null
c1ccccc1
HO-
O1CCCC1
null
2
CC(C)Oc1ccc(C(=O)O)cc1C#N.NN>O1CCCC1>CC(C)Oc1ccc(C(=O)NN)cc1C#N
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-674d5f4a03694de6ac3e816dbc7769c0
BrCC1CCCCC1.O=Cc1ccc(O)cc1>>O=Cc1ccc(OCC2CCCCC2)cc1
BrCC1CCCCC1.C(=O)([O-])[O-].[K+].[K+].OC1=CC=C(C=O)C=C1.BrCC1CCCCC1.C(=O)([O-])[O-].[K+].[K+].BrCC1CCCCC1.C(=O)([O-])[O-].[K+].[K+]>>C1(CCCCC1)COC1=CC=C(C=O)C=C1
Br[CH2:8][CH:9]1[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]1.[O:1]=[CH:2][c:3]1[cH:4][cH:5][c:6]([OH:7])[cH:15][cH:16]1>>[O:1]=[CH:2][c:3]1[cH:4][cH:5][c:6]([O:7][CH2:8][CH:9]2[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]2)[cH:15][cH:16]1
BrCC1CCCCC1.O=Cc1ccc(O)cc1
O=Cc1ccc(OCC2CCCCC2)cc1
null
null
CC#N
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
c1ccc(OCC2CCCCC2)cc1
Br-[CH2;D2;+0:1]-[C:2](-[C:3])-[C:4].[OH;D1;+0:5]-[c:6](:[c:7]):[c:8]>>[C:3]-[C:2](-[CH2;D2;+0:1]-[O;H0;D2;+0:5]-[c:6](:[c:7]):[c:8])-[C:4]
82.5
[{"value": 82.0, "product": "C1(CCCCC1)COC1=CC=C(C=O)C=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 82.5, "product": "C1(CCCCC1)COC1=CC=C(C=O)C=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
null
null
A solution of 4-hydroxybenzaldehyde (0.244 g, 2.00 mmol) in CH3CN (4.0 mL) was treated with bromomethylcyclohexane (0.279 g, 2.00 mmol) and K2CO3 (0.332 g, 2.40 mmol). The reaction mixture was heated to 100° C. for 1 h in a Biotage Initiator microwave synthesizer. Additional bromomethylcyclohexane (0.279 g, 2.00 mmol) ...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccccc1.C1CCCCC1
HBr
CC#N
100
null
BrCC1CCCCC1.O=Cc1ccc(O)cc1>CC#N>O=Cc1ccc(OCC2CCCCC2)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-969c5a80582646b09154468ddd0b1d70
CC(C)Oc1ccc(C(=O)Oc2c(F)c(F)c(F)c(F)c2F)cc1Cl.N#CCCNN.O=Cc1ccc(OCc2ccccc2)cc1>>CC(C)Oc1ccc(C(=O)NN(CCC#N)Cc2ccc(OCc3ccccc3)cc2)cc1Cl
C(C1=CC=CC=C1)OC1=CC=C(C=O)C=C1.C(#N)[BH3-].[Na+].O.C1(=CC=C(C=C1)S(=O)(=O)O)C.ClC=1C=C(C(=O)OC2=C(C(=C(C(=C2F)F)F)F)F)C=CC1OC(C)C.N(N)CCC#N.C(C1=CC=CC=C1)OC1=CC=C(C=O)C=C1.C(#N)[BH3-].[Na+].O.C1(=CC=C(C=C1)S(=O)(=O)O)C>>ClC=1C=C(C(=O)NN(CC2=CC=C(C=C2)OCC2=CC=CC=C2)CCC#N)C=CC1OC(C)C
Fc1c(F)c(F)c(O[C:9]([c:8]2[cH:7][cH:6][c:5]([O:4][CH:2]([CH3:1])[CH3:3])[c:33]([Cl:34])[cH:32]2)=[O:10])c(F)c1F.[NH2:11][NH:12][CH2:13][CH2:14][C:15]#[N:16].O=[CH:17][c:18]1[cH:19][cH:20][c:21]([O:22][CH2:23][c:24]2[cH:25][cH:26][cH:27][cH:28][cH:29]2)[cH:30][cH:31]1>>[CH3:1][CH:2]([CH3:3])[O:4][c:5]1[cH:6][cH:7][c:8](...
CC(C)Oc1ccc(C(=O)Oc2c(F)c(F)c(F)c(F)c2F)cc1Cl.N#CCCNN.O=Cc1ccc(OCc2ccccc2)cc1
CC(C)Oc1ccc(C(=O)NN(CCC#N)Cc2ccc(OCc3ccccc3)cc2)cc1Cl
null
null
CO
Acylation
OtherReaction
4f44b51689e1f4833a0397da7a50cc8df7324d129854859806740bbba48c649d
43d3d2eb9378ed442d985c6d5bfd8e2bbd03cb1a22ded2b68a4ab3785a383157
O=C(NNCc1ccc(OCc2ccccc2)cc1)c1ccccc1
F-c1:c(-F):c(-F):c(-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]):c(-F):c:1-F.O=[CH;D2;+0:6]-[c:7](:[c:8]):[c:9].[C:10]-[C:11]-[NH;D2;+0:12]-[NH2;D1;+0:13]>>[C:10]-[C:11]-[N;H0;D3;+0:12](-[CH2;D2;+0:6]-[c:7](:[c:8]):[c:9])-[NH;D2;+0:13]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
61.3
[{"value": 61.0, "product": "ClC=1C=C(C(=O)NN(CC2=CC=C(C=C2)OCC2=CC=CC=C2)CCC#N)C=CC1OC(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 61.3, "product": "ClC=1C=C(C(=O)NN(CC2=CC=C(C=C2)OCC2=CC=CC=C2)CCC#N)C=CC1OC(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
30
MINUTE
A solution of pentafluorophenyl 3-chloro-4-[(1-methylethyl)oxy]benzoate (0.100 g, 0.263 mmol) in methanol (5.0 mL) was treated with 3-hydrazinopropanenitrile (0.023 mL, 0.289 mmol) and heated to reflux for 1 h. Following cooling, 4-(benzyloxy)benzaldehyde (0.067 g, 0.315 mmol), sodium cyanoborohydride (0.020 g, 0.315 m...
10.6084/m9.figshare.5104873.v1
null
Hydrazine.Aromatic halide.Aromatic halide.Aromatic halide.Aromatic halide.Aromatic halide.Aldehyde.Ester
Acylhydrazine
c1ccccc1
null
c1ccccc1.c1ccccc1.c1ccccc1
HF
CO
null
0.5
CC(C)Oc1ccc(C(=O)Oc2c(F)c(F)c(F)c(F)c2F)cc1Cl.N#CCCNN.O=Cc1ccc(OCc2ccccc2)cc1>CO>CC(C)Oc1ccc(C(=O)NN(CCC#N)Cc2ccc(OCc3ccccc3)cc2)cc1Cl
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-1214585e18644ff0b15cadc6b737a489
C#CCOC.COc1cc2c(Nc3ccc(I)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1>>COCC#Cc1ccc(Nc2ncnc3cc(OCCCN4CCOCC4)c(OC)cc23)c2c1OCO2
C(C)(C)NC(C)C.IC1=CC=C(C2=C1OCO2)NC2=NC=NC1=CC(=C(C=C21)OC)OCCCN2CCOCC2.C(C#C)OC>>COC=1C=C2C(=NC=NC2=CC1OCCCN1CCOCC1)NC1=CC=C(C=2OCOC21)C#CCOC
[CH3:1][O:2][CH2:3][C:4]#[CH:5].I[c:6]1[cH:7][cH:8][c:9]([NH:10][c:11]2[n:12][cH:13][n:14][c:15]3[cH:16][c:17]([O:18][CH2:19][CH2:20][CH2:21][N:22]4[CH2:23][CH2:24][O:25][CH2:26][CH2:27]4)[c:28]([O:29][CH3:30])[cH:31][c:32]23)[c:33]2[c:34]1[O:35][CH2:36][O:37]2>>[CH3:1][O:2][CH2:3][C:4]#[C:5][c:6]1[cH:7][cH:8][c:9]([NH...
C#CCOC.COc1cc2c(Nc3ccc(I)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1
COCC#Cc1ccc(Nc2ncnc3cc(OCCCN4CCOCC4)c(OC)cc23)c2c1OCO2
null
Cl[Pd]([P](C1=CC=CC=C1)(C2=CC=CC=C2)C3=CC=CC=C3)([P](C4=CC=CC=C4)(C5=CC=CC=C5)C6=CC=CC=C6)Cl.[Cu](I)I
C(C)(=O)OCC
C-C Coupling
Sonogashira alkyne_aryl halide
4fe05dd9f4e06ca437f6fd540183d70cbf88cbb037b34a93217c201e7139cd32
305eca0fd2975da49e7f69e4edfb9dc1cbce82513954bc5a73be3289e70e5f76
c1cc(Nc2ncnc3cc(OCCCN4CCOCC4)ccc23)c2c(c1)OCO2
I-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]1:[c:5]-[#8:6]-[C:7]-[#8:8]-1.[C:9]-[C:10]#[CH;D1;+0:11]>>[C:9]-[C:10]#[C;H0;D2;+0:11]-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]1:[c:5]-[#8:6]-[C:7]-[#8:8]-1
30.6
[{"value": 30.6, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCOCC1)NC1=CC=C(C=2OCOC21)C#CCOC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
16
HOUR
Bis(Triphenyl-phosphine)palladium(II) chloride (94 mg), copper iodide (19 mg) and diisopropylamine (68 mg) were added to a stirred solution of N-(7-iodo-1,3-benzodioxol-4-yl)-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amine (200 mg) and methyl propargyl ether (47 mg) in ethyl acetate (5 mls) at −20° C. The react...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Alkyne
Alkyne
c1ccc2c(c1)OCO2
c1ccc2c(c1)OCO2
c1ccc2ncncc2c1.C1COCC[NH]1.c1ccc2c(c1)OCO2
HI
Cl[Pd]([P](C1=CC=CC=C1)(C2=CC=CC=C2)C3=CC=CC=C3)([P](C4=CC=CC=C4)(C5=CC=CC=C5)C6=CC=CC=C6)Cl.[Cu](I)I.C(C)(=O)OCC
null
16
C#CCOC.COc1cc2c(Nc3ccc(I)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1>Cl[Pd]([P](C1=CC=CC=C1)(C2=CC=CC=C2)C3=CC=CC=C3)([P](C4=CC=CC=C4)(C5=CC=CC=C5)C6=CC=CC=C6)Cl.[Cu](I)I.C(C)(=O)OCC>COCC#Cc1ccc(Nc2ncnc3cc(OCCCN4CCOCC4)c(OC)cc23)c2c1OCO2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-dc31d262ef28486bb411c7e7a1c90a3a
CO.O=C(O)c1cccc(O)c1O>>COC(=O)c1cccc(O)c1O
OC1=C(C(=O)O)C=CC=C1O.CO>>OC1=C(C(=O)OC)C=CC=C1O
[CH3:1][OH:2].O[C:3](=[O:4])[c:5]1[cH:6][cH:7][cH:8][c:9]([OH:10])[c:11]1[OH:12]>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][cH:8][c:9]([OH:10])[c:11]1[OH:12]
CO.O=C(O)c1cccc(O)c1O
COC(=O)c1cccc(O)c1O
null
S(O)(O)(=O)=O
null
Protection
Esterification of Carboxylic Acids
9cecdbd189c6f9c3648521d17154d013842a5498de4e76e65efb1d842973340b
af0b8064f2e82ebe66c4c29d2391785ac1b993104265ccdc4d67ca79e36fa3c8
c1ccccc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C;D1;H3:6]-[OH;D1;+0:7]>>[C;D1;H3:6]-[O;H0;D2;+0:7]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
null
[]
60
CELSIUS
null
null
A mixture of 2,3-dihydroxybenzoic acid (5 g), methanol (50 ml) and concentrated sulphuric acid (10 drops) was stirred and heated to 60° C. for 24 hours. The mixture was evaporated and the residue was taken up in ethyl acetate. The organic solution was washed with a saturated solution of sodium bicarbonate, dried over m...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Methanol
Ester
null
null
c1ccccc1
HO-
S(O)(O)(=O)=O
60
null
CO.O=C(O)c1cccc(O)c1O>S(O)(O)(=O)=O>COC(=O)c1cccc(O)c1O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-689ca49645354ed7b4eb7185c06147f4
Nc1cccc2c1OCO2>>Nc1ccc(I)c2c1OCO2
I(=O)(=O)Cl.I(=O)(=O)Cl.C(C1=CC=CC=C1)[N+](C)(C)C.O1COC2=C1C=CC=C2N.C([O-])([O-])=O.[Ca+2]>>IC1=CC=C(C2=C1OCO2)N
[NH2:1][c:2]1[cH:3][cH:4][cH:5][c:7]2[c:8]1[O:9][CH2:10][O:11]2>>[NH2:1][c:2]1[cH:3][cH:4][c:5]([I:6])[c:7]2[c:8]1[O:9][CH2:10][O:11]2
Nc1cccc2c1OCO2
Nc1ccc(I)c2c1OCO2
null
null
ClCCl.O.CO
Functional Group Addition
Aromatic iodination
6ba82dee4826ea9605d6e45f3fbe0149be15f482d7d85b7cfe266d92504d953d
0a2f22058f27970cef4a98a778644dbe9c44e91f66c74cd24db321993177608a
c1ccc2c(c1)OCO2
[c:1]:[c:2]:[cH;D2;+0:3]:[c:4]1:[c:5]-[#8:6]-[C:7]-[#8:8]-1>>[I;D1;H0:9]-[c;H0;D3;+0:3](:[c:2]:[c:1]):[c:4]1:[c:5]-[#8:6]-[C:7]-[#8:8]-1
null
[]
null
null
1.5
HOUR
Benzyltrimethylammonium dichloroiodate (2.8 g) was added portionwise over 10 minutes to a stirred mixture of 1,3-benzodioxol-4-amine (1 g), calcium carbonate (0.95 g) in methanol (5 ml) and dichloromethane (10 ml). The reaction mixture was stirred at ambient temperature for 1.5 hours. The reaction mixture was diluted w...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ccc2c(c1)OCO2
c1ccc2c(c1)OCO2
c1ccc2c(c1)OCO2
Other
ClCCl.O.CO
null
1.5
Nc1cccc2c1OCO2>ClCCl.O.CO>Nc1ccc(I)c2c1OCO2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-1fdd00c07e954c4ea497c729e85dc65b
COc1cc(C(N)=O)c(N)cc1OCc1ccccc1>>COc1cc2c(=O)[nH]cnc2cc1OCc1ccccc1
NC1=C(C(=O)N)C=C(C(=C1)OCC1=CC=CC=C1)OC.[Cl-].CN(C=NC=[N+](C)C)C.O1CCOCC1.C(C)(=O)[O-].[Na+]>>C(C1=CC=CC=C1)OC1=C(C=C2C(NC=NC2=C1)=O)OC
[CH3:1][O:2][c:3]1[cH:4][c:5]([C:6](=[O:7])[NH2:8])[c:11]([NH2:10])[cH:12][c:13]1[O:14][CH2:15][c:16]1[cH:17][cH:18][cH:19][cH:20][cH:21]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6](=[O:7])[nH:8][cH:9][n:10][c:11]2[cH:12][c:13]1[O:14][CH2:15][c:16]1[cH:17][cH:18][cH:19][cH:20][cH:21]1
COc1cc(C(N)=O)c(N)cc1OCc1ccccc1
COc1cc2c(=O)[nH]cnc2cc1OCc1ccccc1
null
null
C(C)(=O)O
Aromatic Heterocycle Formation
OtherReaction
0798449d56bc7e7756a703d33bd60780d26c4986e39e1809e15228456c95135b
3074b6c74bc99545969aa05d42dae7b149d9d6bb1b36a52cec3a362e1e7f7ca0
O=c1[nH]cnc2cc(OCc3ccccc3)ccc12
[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4](-[C;H0;D3;+0:5](-[NH2;D1;+0:6])=[O;D1;H0:7]):[c:8]>>[O;D1;H0:7]=[c;H0;D3;+0:5]1:[nH;D2;+0:6]:[c:9]:[n;H0;D2;+0:1]:[c:2](:[c:3]):[c:4]:1:[c:8]
83.9
[{"value": 83.9, "product": "C(C1=CC=CC=C1)OC1=C(C=C2C(NC=NC2=C1)=O)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A mixture of 2-amino-4-benzyloxy-5-methoxybenzamide (J. Med. Chem., 1977, 20, 146-149; 10 g), (3-dimethylamino-2-azaprop-2-en-1-ylidene)dimethylammonium chloride (Gold's reagent, 7.4 g) and dioxane (100 ml) was stirred and heated to reflux for 24 hours. Sodium acetate (3.02 g) and acetic acid (1.65 ml) were added and t...
10.6084/m9.figshare.5104873.v1
null
Primary amide.Primary amine
null
c1ccccc1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.c1ccccc1
Other
C(C)(=O)O
null
null
COc1cc(C(N)=O)c(N)cc1OCc1ccccc1>C(C)(=O)O>COc1cc2c(=O)[nH]cnc2cc1OCc1ccccc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-e8eb7f267ef34b4f88c5382363ff5b97
COc1cc2c(=O)[nH]cnc2cc1OCc1ccccc1.O=S(Cl)Cl>>COc1cc2c(Cl)ncnc2cc1OCc1ccccc1
C(C1=CC=CC=C1)OC1=C(C=C2C(NC=NC2=C1)=O)OC.S(=O)(Cl)Cl>>C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)Cl)OC
O=[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:13]([O:14][CH2:15][c:16]3[cH:17][cH:18][cH:19][cH:20][cH:21]3)[cH:12][c:11]2[n:10][cH:9][nH:8]1.O=S(Cl)[Cl:7]>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([Cl:7])[n:8][cH:9][n:10][c:11]2[cH:12][c:13]1[O:14][CH2:15][c:16]1[cH:17][cH:18][cH:19][cH:20][cH:21]1
COc1cc2c(=O)[nH]cnc2cc1OCc1ccccc1.O=S(Cl)Cl
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1
null
null
CN(C)C=O
Functional Group Interconversion
OtherReaction
3788560e87eee8765e749543914a91a512631307b97fad163ebef894d2a0ea68
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
c1ccc(COc2ccc3cncnc3c2)cc1
Cl-S(=O)-[Cl;H0;D1;+0:1].O=[c;H0;D3;+0:2]1:[nH;D2;+0:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9]>>[Cl;H0;D1;+0:1]-[c;H0;D3;+0:2]1:[n;H0;D2;+0:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9]
null
[]
null
null
null
null
After repetition of the reaction so described, a mixture of 7-benzyloxy-6-methoxy-3,4-dihydroquinazolin-4-one (35 g), thionyl chloride (440 ml) and DMF (1.75 ml) was heated to reflux for 4 hours. The thionyl chloride was evaporated under vacuum and the residue was azeotroped with toluene three times. The residue was di...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.c1ccccc1
HCl
CN(C)C=O
null
null
COc1cc2c(=O)[nH]cnc2cc1OCc1ccccc1.O=S(Cl)Cl>CN(C)C=O>COc1cc2c(Cl)ncnc2cc1OCc1ccccc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3228802d071348aba37b9700ebabcbe4
C1COCCN1.ClCCCBr>>ClCCCN1CCOCC1
N1CCOCC1.BrCCCCl>>O1CCN(CC1)CCCCl
[NH:5]1[CH2:6][CH2:7][O:8][CH2:9][CH2:10]1.Br[CH2:4][CH2:3][CH2:2][Cl:1]>>[Cl:1][CH2:2][CH2:3][CH2:4][N:5]1[CH2:6][CH2:7][O:8][CH2:9][CH2:10]1
C1COCCN1.ClCCCBr
ClCCCN1CCOCC1
null
null
C1(=CC=CC=C1)C
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
2bad30dcdb0a20edb8ce877f072b133eedfd870621da393ec393128bfee00977
523d37155b42c8dc851abeddadebb241cdd90bdf649ba750c35e13c8c752d7b0
C1COCCN1
Br-[CH2;D2;+0:1]-[C:2]-[C:3].[#8:4]1-[C:5]-[C:6]-[NH;D2;+0:7]-[C:8]-[C:9]-1>>[C:3]-[C:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:7]1-[C:8]-[C:9]-[#8:4]-[C:5]-[C:6]-1
null
[]
70
CELSIUS
null
null
A mixture of morpholine (52.2 ml), 1-bromo-3-chloropropane (30 ml) and toluene (180 ml) was heated to 70° C. for 3 hours. The solid was removed by filtration and the filtrate was evaporated under vacuum. The resultant oil was decanted from the additional solid which was deposited and the oil was purified by vacuum dist...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amine
Tertiary amine
C1COCCN1
C1COCC[NH]1
C1COCC[NH]1
HBr
C1(=CC=CC=C1)C
70
null
C1COCCN1.ClCCCBr>C1(=CC=CC=C1)C>ClCCCN1CCOCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-7a504a42da584de49401a76c01ed7ad0
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Nc1ccc(I)c2c1OCO2>>COc1cc2c(Nc3ccc(I)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1
Cl.ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1.IC1=CC=C(C2=C1OCO2)N>>IC1=CC=C(C2=C1OCO2)NC2=NC=NC1=CC(=C(C=C21)OC)OCCCN2CCOCC2
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:23]([O:24][CH2:25][CH2:26][CH2:27][N:28]3[CH2:29][CH2:30][O:31][CH2:32][CH2:33]3)[cH:22][c:21]2[n:20][cH:19][n:18]1.[NH2:7][c:8]1[cH:9][cH:10][c:11]([I:12])[c:13]2[c:14]1[O:15][CH2:16][O:17]2>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([NH:7][c:8]3[cH:9][cH:10][c:11]([I:12])[c:13]4[c:...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Nc1ccc(I)c2c1OCO2
COc1cc2c(Nc3ccc(I)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1
null
null
O1CCOCC1.CC(=O)N(C)C
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
94bd1d6b149f0eabeae34be7987089f25636bc079a6d701a568fe61e8bfdb7f3
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1cc(Nc2ncnc3cc(OCCCN4CCOCC4)ccc23)c2c(c1)OCO2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#8:9]-[c:10]:[c:11](-[NH2;D1;+0:12]):[c:13]>>[#8:9]-[c:10]:[c:11](-[NH;D2;+0:12]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:13]
70.6
[{"value": 70.6, "product": "IC1=CC=C(C2=C1OCO2)NC2=NC=NC1=CC(=C(C=C21)OC)OCCCN2CCOCC2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
80
CELSIUS
null
null
4.0M HCl in Dioxane (0.37 ml) was added to a stirred suspension of 4-chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline (500 mg) and 7-iodo-1,3-benzodioxol-4-amine (0.39 g) in DMA (1 ml). The resultant mixture was stirred and heated to 80° C. for 10 mins. A grey precipitate was formed which was filtered and washed...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2c(c1)OCO2.c1ccc2ncncc2c1.C1COCC[NH]1
HCl
O1CCOCC1.CC(=O)N(C)C
80
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Nc1ccc(I)c2c1OCO2>O1CCOCC1.CC(=O)N(C)C>COc1cc2c(Nc3ccc(I)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-977e051cf17b49c0acda6249e6ba60e5
COCC#Cc1cc(Cl)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1>>COCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCOCC4)c(OC)cc23)c2c1OCO2
C[Si](N[Si](C)(C)C)(C)C.[Na].ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1.ClC1=C(C2=C(OCO2)C(=C1)C#CCOC)N>>ClC1=C(C2=C(OCO2)C(=C1)C#CCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1
[CH3:1][O:2][CH2:3][C:4]#[C:5][c:6]1[cH:7][c:8]([Cl:9])[c:10]([NH2:11])[c:34]2[c:35]1[O:36][CH2:37][O:38]2.Cl[c:12]1[n:13][cH:14][n:15][c:16]2[cH:17][c:18]([O:19][CH2:20][CH2:21][CH2:22][N:23]3[CH2:24][CH2:25][O:26][CH2:27][CH2:28]3)[c:29]([O:30][CH3:31])[cH:32][c:33]12>>[CH3:1][O:2][CH2:3][C:4]#[C:5][c:6]1[cH:7][c:8](...
COCC#Cc1cc(Cl)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1
COCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCOCC4)c(OC)cc23)c2c1OCO2
null
null
CC(=O)N(C)C
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
94bd1d6b149f0eabeae34be7987089f25636bc079a6d701a568fe61e8bfdb7f3
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1cc(Nc2ncnc3cc(OCCCN4CCOCC4)ccc23)c2c(c1)OCO2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#8:9]-[c:10]:[c:11](-[NH2;D1;+0:12]):[c:13]>>[#8:9]-[c:10]:[c:11](-[NH;D2;+0:12]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:13]
72.2
[{"value": 72.2, "product": "ClC1=C(C2=C(OCO2)C(=C1)C#CCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
null
null
Sodium hexamethyldisilazane (1M solution in THF; 1.0 ml) was added to a mixture of 4-chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline (0.16 g) and 5-chloro-7-(3-methoxyprop-1-ynyl)-1,3-benzodioxol-4-amine (0.12 g) in DMA (5 ml) that was cooled to 0° C. The resultant mixture was stirred and allowed to warm to amb...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.C1COCC[NH]1.c1ccc2c(c1)OCO2
HCl
CC(=O)N(C)C
0
null
COCC#Cc1cc(Cl)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1>CC(=O)N(C)C>COCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCOCC4)c(OC)cc23)c2c1OCO2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-91b21b00d834420dbe555ee53af2550b
C#CCOC.Nc1c(Cl)cc(I)c2c1OCO2>>COCC#Cc1cc(Cl)c(N)c2c1OCO2
C(C)(C)NC(C)C.ClC1=C(C2=C(OCO2)C(=C1)I)N.C(C#C)OC>>ClC1=C(C2=C(OCO2)C(=C1)C#CCOC)N
[CH3:1][O:2][CH2:3][C:4]#[CH:5].I[c:6]1[cH:7][c:8]([Cl:9])[c:10]([NH2:11])[c:12]2[c:13]1[O:14][CH2:15][O:16]2>>[CH3:1][O:2][CH2:3][C:4]#[C:5][c:6]1[cH:7][c:8]([Cl:9])[c:10]([NH2:11])[c:12]2[c:13]1[O:14][CH2:15][O:16]2
C#CCOC.Nc1c(Cl)cc(I)c2c1OCO2
COCC#Cc1cc(Cl)c(N)c2c1OCO2
null
Cl[Pd]([P](C1=CC=CC=C1)(C2=CC=CC=C2)C3=CC=CC=C3)([P](C4=CC=CC=C4)(C5=CC=CC=C5)C6=CC=CC=C6)Cl.[Cu](I)I
C(C)(=O)OCC
C-C Coupling
Sonogashira alkyne_aryl halide
4fe05dd9f4e06ca437f6fd540183d70cbf88cbb037b34a93217c201e7139cd32
305eca0fd2975da49e7f69e4edfb9dc1cbce82513954bc5a73be3289e70e5f76
c1ccc2c(c1)OCO2
I-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]1:[c:5]-[#8:6]-[C:7]-[#8:8]-1.[C:9]-[C:10]#[CH;D1;+0:11]>>[C:9]-[C:10]#[C;H0;D2;+0:11]-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]1:[c:5]-[#8:6]-[C:7]-[#8:8]-1
null
[]
null
null
null
null
Bis(Triphenyl-phosphine)palladium(II) chloride (472 mg), copper iodide (192 mg) and diisopropylamine (680 mg) were added to a stirred solution of 5-chloro-7-iodo-1,3-benzodioxol-4-amine (1000 mg) and methyl propargyl ether (471 mg) in ethyl acetate (10 mls) at −20° C. The reaction was allowed to warm to ambient tempera...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Alkyne
Alkyne
c1ccc2c(c1)OCO2
c1ccc2c(c1)OCO2
c1ccc2c(c1)OCO2
HI
Cl[Pd]([P](C1=CC=CC=C1)(C2=CC=CC=C2)C3=CC=CC=C3)([P](C4=CC=CC=C4)(C5=CC=CC=C5)C6=CC=CC=C6)Cl.[Cu](I)I.C(C)(=O)OCC
null
null
C#CCOC.Nc1c(Cl)cc(I)c2c1OCO2>Cl[Pd]([P](C1=CC=CC=C1)(C2=CC=CC=C2)C3=CC=CC=C3)([P](C4=CC=CC=C4)(C5=CC=CC=C5)C6=CC=CC=C6)Cl.[Cu](I)I.C(C)(=O)OCC>COCC#Cc1cc(Cl)c(N)c2c1OCO2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-4708001b55df41498dd9dd946d2cabec
COCC#Cc1cc(Cl)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(C)CC1>>COCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCN(C)CC4)c(OC)cc23)c2c1OCO2
C[Si](C)(C)[N-][Si](C)(C)C.[Na+].O1CCCC1.ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCN(CC1)C.ClC1=C(C2=C(OCO2)C(=C1)C#CCOC)N>>COC=1C=C2C(=NC=NC2=CC1OCCCN1CCN(CC1)C)NC1=C(C=C(C=2OCOC21)C#CCOC)Cl
[CH3:1][O:2][CH2:3][C:4]#[C:5][c:6]1[cH:7][c:8]([Cl:9])[c:10]([NH2:11])[c:35]2[c:36]1[O:37][CH2:38][O:39]2.Cl[c:12]1[n:13][cH:14][n:15][c:16]2[cH:17][c:18]([O:19][CH2:20][CH2:21][CH2:22][N:23]3[CH2:24][CH2:25][N:26]([CH3:27])[CH2:28][CH2:29]3)[c:30]([O:31][CH3:32])[cH:33][c:34]12>>[CH3:1][O:2][CH2:3][C:4]#[C:5][c:6]1[c...
COCC#Cc1cc(Cl)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(C)CC1
COCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCN(C)CC4)c(OC)cc23)c2c1OCO2
null
null
[Cl-].[NH4+].CN(C)C=O
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
94bd1d6b149f0eabeae34be7987089f25636bc079a6d701a568fe61e8bfdb7f3
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1cc(Nc2ncnc3cc(OCCCN4CCNCC4)ccc23)c2c(c1)OCO2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#8:9]-[c:10]:[c:11](-[NH2;D1;+0:12]):[c:13]>>[#8:9]-[c:10]:[c:11](-[NH;D2;+0:12]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:13]
65.7
[{"value": 65.7, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCN(CC1)C)NC1=C(C=C(C=2OCOC21)C#CCOC)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
1.5
HOUR
A solution of sodium bis(trimethylsilyl)amide (1.33 ml) in tetrahydrofuran (1.0 Mol/L, 1.33 mmol) was added to a solution of 4-chloro-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazoline (0.212 g) and 5-chloro-7-(3-methoxyprop-1-ynyl)-1,3-benzodioxol-4-amine (0.16 g) in DMF (3 ml) cooled to 0° C. under a nitrogen...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.C1C[NH]CC[NH]1.c1ccc2c(c1)OCO2
HCl
[Cl-].[NH4+].CN(C)C=O
0
1.5
COCC#Cc1cc(Cl)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(C)CC1>[Cl-].[NH4+].CN(C)C=O>COCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCN(C)CC4)c(OC)cc23)c2c1OCO2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-b46ce9e6979b4ab6819c04f86aa029d8
CN1CCNCC1.OCCCBr>>CN1CCN(CCCO)CC1
BrCCCO.CN1CCNCC1.C([O-])([O-])=O.[K+].[K+]>>OCCCN1CCN(CC1)C
[CH3:1][N:2]1[CH2:3][CH2:4][NH:5][CH2:10][CH2:11]1.Br[CH2:6][CH2:7][CH2:8][OH:9]>>[CH3:1][N:2]1[CH2:3][CH2:4][N:5]([CH2:6][CH2:7][CH2:8][OH:9])[CH2:10][CH2:11]1
CN1CCNCC1.OCCCBr
CN1CCN(CCCO)CC1
null
null
C(C)O
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
b703623ddc3b029d4716c15f5414f41773434bcc7e3f3853faf62273596bed77
523d37155b42c8dc851abeddadebb241cdd90bdf649ba750c35e13c8c752d7b0
C1CNCCN1
Br-[CH2;D2;+0:1]-[C:2]-[C:3].[#7:4]1-[C:5]-[C:6]-[NH;D2;+0:7]-[C:8]-[C:9]-1>>[C:3]-[C:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:7]1-[C:6]-[C:5]-[#7:4]-[C:9]-[C:8]-1
null
[]
null
null
null
null
A mixture of 3-bromopropanol (20 ml), N-methylpiperazine (29 ml), potassium carbonate (83 g) and ethanol (200 ml)was stirred and heated to reflux for 20 hours. The mixture was cooled to ambient temperature and filtered. The filtrate was evaporated and the residue was triturated under diethyl ether. The resultant mixtur...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amine
Tertiary amine
C1C[NH]CCN1
C1C[NH]CC[NH]1
C1C[NH]CC[NH]1
HBr
C(C)O
null
null
CN1CCNCC1.OCCCBr>C(C)O>CN1CCN(CCCO)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-aedeedf1385e407d97a14ec9f40f6b3f
CN1CCN(CCCO)CC1.Cc1ccc(S(=O)(=O)Cl)cc1>>Cc1ccc(S(=O)(=O)OCCCN2CCN(C)CC2)cc1
C1(=CC=C(C=C1)S(=O)(=O)Cl)C.OCCCN1CCN(CC1)C.C(C)N(CC)CC>>C1(=CC=C(C=C1)S(=O)(=O)OCCCN1CCN(CC1)C)C
[OH:9][CH2:10][CH2:11][CH2:12][N:13]1[CH2:14][CH2:15][N:16]([CH3:17])[CH2:18][CH2:19]1.Cl[S:6]([c:5]1[cH:4][cH:3][c:2]([CH3:1])[cH:21][cH:20]1)(=[O:7])=[O:8]>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([S:6](=[O:7])(=[O:8])[O:9][CH2:10][CH2:11][CH2:12][N:13]2[CH2:14][CH2:15][N:16]([CH3:17])[CH2:18][CH2:19]2)[cH:20][cH:21]1
CN1CCN(CCCO)CC1.Cc1ccc(S(=O)(=O)Cl)cc1
Cc1ccc(S(=O)(=O)OCCCN2CCN(C)CC2)cc1
null
null
C(Cl)Cl
Acylation
Formation of Sulfonic Esters
d05d91207659f8fa672c205a316a670adfe2b92492fc9adad2ee3f241e574fb9
a7748b0f3b0eba3868d0cf03ae67721db046202accaaea9cadb4edbc96ec8768
O=S(=O)(OCCCN1CCNCC1)c1ccccc1
Cl-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[c:4](:[c:5]):[c:6].[C:7]-[C:8]-[OH;D1;+0:9]>>[C:7]-[C:8]-[O;H0;D2;+0:9]-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[c:4](:[c:5]):[c:6]
null
[]
null
null
null
null
4-Toluenesulphonyl chloride (3.2 g) was added to a stirred mixture of 1-(3-hydroxypropyl)-4-methylpiperazine (2.4 g), triethylamine (4.6 ml) and methylene chloride (60 ml) and the resultant mixture was stirred at ambient temperature for 2 hours. The solution was washed in turn with a saturated aqueous sodium bicarbonat...
10.6084/m9.figshare.5104873.v1
null
Tosylate.Primary alcohol.Sulfonyl halide
Tosylate
null
null
c1ccccc1.C1C[NH]CC[NH]1
HCl
C(Cl)Cl
null
null
CN1CCN(CCCO)CC1.Cc1ccc(S(=O)(=O)Cl)cc1>C(Cl)Cl>Cc1ccc(S(=O)(=O)OCCCN2CCN(C)CC2)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-2ac602cf09f74dc2b42b2152ae962975
COc1cc(C(N)=O)c(N)cc1OCc1ccccc1>>COc1cc2c(=O)[nH]cnc2cc1OCc1ccccc1
NC1=C(C(=O)N)C=C(C(=C1)OCC1=CC=CC=C1)OC.[Cl-].CN(C=NC=[N+](C)C)C.O1CCOCC1.C(C)(=O)[O-].[Na+]>>C(C1=CC=CC=C1)OC1=C(C=C2C(NC=NC2=C1)=O)OC
[CH3:1][O:2][c:3]1[cH:4][c:5]([C:6](=[O:7])[NH2:8])[c:11]([NH2:10])[cH:12][c:13]1[O:14][CH2:15][c:16]1[cH:17][cH:18][cH:19][cH:20][cH:21]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6](=[O:7])[nH:8][cH:9][n:10][c:11]2[cH:12][c:13]1[O:14][CH2:15][c:16]1[cH:17][cH:18][cH:19][cH:20][cH:21]1
COc1cc(C(N)=O)c(N)cc1OCc1ccccc1
COc1cc2c(=O)[nH]cnc2cc1OCc1ccccc1
null
null
C(C)(=O)O
Aromatic Heterocycle Formation
OtherReaction
0798449d56bc7e7756a703d33bd60780d26c4986e39e1809e15228456c95135b
3074b6c74bc99545969aa05d42dae7b149d9d6bb1b36a52cec3a362e1e7f7ca0
O=c1[nH]cnc2cc(OCc3ccccc3)ccc12
[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4](-[C;H0;D3;+0:5](-[NH2;D1;+0:6])=[O;D1;H0:7]):[c:8]>>[O;D1;H0:7]=[c;H0;D3;+0:5]1:[nH;D2;+0:6]:[c:9]:[n;H0;D2;+0:1]:[c:2](:[c:3]):[c:4]:1:[c:8]
83.9
[{"value": 83.9, "product": "C(C1=CC=CC=C1)OC1=C(C=C2C(NC=NC2=C1)=O)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A mixture of 2-amino-4-benzyloxy-5-methoxybenzamide (J. Med. Chem., 1977, 20, 146-149; 10 g), (3-dimethylamino-2-azaprop-2-en-1-ylidene)dimethylammonium chloride (Gold's reagent, 7.4 g) and dioxane (100 ml) was stirred and heated to reflux for 24 hours. Sodium acetate (3.02 g) and acetic acid (1.65 ml) were added and t...
10.6084/m9.figshare.5104873.v1
null
Primary amide.Primary amine
null
c1ccccc1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.c1ccccc1
Other
C(C)(=O)O
null
null
COc1cc(C(N)=O)c(N)cc1OCc1ccccc1>C(C)(=O)O>COc1cc2c(=O)[nH]cnc2cc1OCc1ccccc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-d9975e79f132408fb3402d78e1cb5a69
COc1cc2c(=O)[nH]cnc2cc1OCc1ccccc1.O=S(Cl)Cl>>COc1cc2c(Cl)ncnc2cc1OCc1ccccc1
C(C1=CC=CC=C1)OC1=C(C=C2C(NC=NC2=C1)=O)OC.S(=O)(Cl)Cl>>C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)Cl)OC
O=[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:13]([O:14][CH2:15][c:16]3[cH:17][cH:18][cH:19][cH:20][cH:21]3)[cH:12][c:11]2[n:10][cH:9][nH:8]1.O=S(Cl)[Cl:7]>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([Cl:7])[n:8][cH:9][n:10][c:11]2[cH:12][c:13]1[O:14][CH2:15][c:16]1[cH:17][cH:18][cH:19][cH:20][cH:21]1
COc1cc2c(=O)[nH]cnc2cc1OCc1ccccc1.O=S(Cl)Cl
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1
null
null
CN(C)C=O
Functional Group Interconversion
OtherReaction
3788560e87eee8765e749543914a91a512631307b97fad163ebef894d2a0ea68
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
c1ccc(COc2ccc3cncnc3c2)cc1
Cl-S(=O)-[Cl;H0;D1;+0:1].O=[c;H0;D3;+0:2]1:[nH;D2;+0:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9]>>[Cl;H0;D1;+0:1]-[c;H0;D3;+0:2]1:[n;H0;D2;+0:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9]
null
[]
null
null
null
null
After repetition of the reaction so described, a mixture of 7-benzyloxy-6-methoxy-3,4-dihydroquinazolin-4-one (20.3 g), thionyl chloride (440 ml) and DMF (1.75 ml) was heated to reflux for4 hours. The thionyl chloride was evaporated under vacuum and the residue was azeotroped with toluene three times to give 7-benzylox...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.c1ccccc1
HCl
CN(C)C=O
null
null
COc1cc2c(=O)[nH]cnc2cc1OCc1ccccc1.O=S(Cl)Cl>CN(C)C=O>COc1cc2c(Cl)ncnc2cc1OCc1ccccc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-9a06e974057146cbb001ce968350b1b5
COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCN(C)CC1.O=S(Cl)Cl>>COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(C)CC1
COC=1C=C2C(NC=NC2=CC1OCCCN1CCN(CC1)C)=O.S(=O)(Cl)Cl>>ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCN(CC1)C
O=[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:13]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:19][CH2:20][N:21]([CH3:22])[CH2:23][CH2:24]3)[cH:12][c:11]2[n:10][cH:9][nH:8]1.O=S(Cl)[Cl:7]>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([Cl:7])[n:8][cH:9][n:10][c:11]2[cH:12][c:13]1[O:14][CH2:15][CH2:16][CH2:17][N:18]1[CH2:19][CH2:20][N:2...
COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCN(C)CC1.O=S(Cl)Cl
COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(C)CC1
null
null
CN(C)C=O
Functional Group Interconversion
OtherReaction
3788560e87eee8765e749543914a91a512631307b97fad163ebef894d2a0ea68
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
c1ncc2ccc(OCCCN3CCNCC3)cc2n1
Cl-S(=O)-[Cl;H0;D1;+0:1].O=[c;H0;D3;+0:2]1:[nH;D2;+0:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9]>>[Cl;H0;D1;+0:1]-[c;H0;D3;+0:2]1:[n;H0;D2;+0:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9]
null
[]
null
null
null
null
After repetition of the previous reaction, a mixture of 6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]-3,4-dihydroquinazolin-4-one (2.15 g), thionyl chloride (25 ml) and DMF (0.18 ml) was stirred and heated to reflux for 2 hours. The thionyl chloride was evaporated under vacuum and the residue azeotroped twice with to...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.C1C[NH]CC[NH]1
HCl
CN(C)C=O
null
null
COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCN(C)CC1.O=S(Cl)Cl>CN(C)C=O>COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(C)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-6dece205276a4b6fab876c8abbd09338
COCC#Cc1cc(F)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1>>COCC#Cc1cc(F)c(Nc2ncnc3cc(OCCCN4CCOCC4)c(OC)cc23)c2c1OCO2
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1.FC1=C(C2=C(OCO2)C(=C1)C#CCOC)N.C[Si](C)(C)[N-][Si](C)(C)C.[Na+]>>FC1=C(C2=C(OCO2)C(=C1)C#CCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1
[CH3:1][O:2][CH2:3][C:4]#[C:5][c:6]1[cH:7][c:8]([F:9])[c:10]([NH2:11])[c:34]2[c:35]1[O:36][CH2:37][O:38]2.Cl[c:12]1[n:13][cH:14][n:15][c:16]2[cH:17][c:18]([O:19][CH2:20][CH2:21][CH2:22][N:23]3[CH2:24][CH2:25][O:26][CH2:27][CH2:28]3)[c:29]([O:30][CH3:31])[cH:32][c:33]12>>[CH3:1][O:2][CH2:3][C:4]#[C:5][c:6]1[cH:7][c:8]([...
COCC#Cc1cc(F)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1
COCC#Cc1cc(F)c(Nc2ncnc3cc(OCCCN4CCOCC4)c(OC)cc23)c2c1OCO2
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
94bd1d6b149f0eabeae34be7987089f25636bc079a6d701a568fe61e8bfdb7f3
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1cc(Nc2ncnc3cc(OCCCN4CCOCC4)ccc23)c2c(c1)OCO2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#8:9]-[c:10]:[c:11](-[NH2;D1;+0:12]):[c:13]>>[#8:9]-[c:10]:[c:11](-[NH;D2;+0:12]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:13]
78
[{"value": 78.0, "product": "FC1=C(C2=C(OCO2)C(=C1)C#CCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 77.8, "product": "FC1=C(C2=C(OCO2)C(=C1)C#CCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
90
MINUTE
4-Chloro-6-methoxy-7-(3-morpholin-4ylpropoxy)quinazoline (201 mg, 0.60 mmol) and 5-fluoro-7-(3-methoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-amine (140 mg, 0.63 mmol) in DMF (3 ml) were cooled in an ice-water bath then treated dropwise, under an atmosphere of nitrogen, with a solution of sodium bis(trimethylsilyl)amide (1.0...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.C1COCC[NH]1.c1ccc2c(c1)OCO2
HCl
CN(C)C=O
null
1.5
COCC#Cc1cc(F)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1>CN(C)C=O>COCC#Cc1cc(F)c(Nc2ncnc3cc(OCCCN4CCOCC4)c(OC)cc23)c2c1OCO2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a0bb6e202603404c829e87cd57f5bc37
Nc1c(F)ccc2c1OCO2>>Nc1c(F)cc(I)c2c1OCO2
FC1=C(C2=C(OCO2)C=C1)N.I(=O)(=O)Cl.I(=O)(=O)Cl.C(C1=CC=CC=C1)[N+](C)(C)C.C([O-])([O-])=O.[Ca+2]>>NC1=C(C=C(C=2OCOC21)I)F
[NH2:1][c:2]1[c:3]([F:4])[cH:5][cH:6][c:8]2[c:9]1[O:10][CH2:11][O:12]2>>[NH2:1][c:2]1[c:3]([F:4])[cH:5][c:6]([I:7])[c:8]2[c:9]1[O:10][CH2:11][O:12]2
Nc1c(F)ccc2c1OCO2
Nc1c(F)cc(I)c2c1OCO2
null
null
ClCCl.CO
Functional Group Addition
Aromatic iodination
6ba82dee4826ea9605d6e45f3fbe0149be15f482d7d85b7cfe266d92504d953d
0a2f22058f27970cef4a98a778644dbe9c44e91f66c74cd24db321993177608a
c1ccc2c(c1)OCO2
[c:1]:[c:2]:[cH;D2;+0:3]:[c:4]1:[c:5]-[#8:6]-[C:7]-[#8:8]-1>>[I;D1;H0:9]-[c;H0;D3;+0:3](:[c:2]:[c:1]):[c:4]1:[c:5]-[#8:6]-[C:7]-[#8:8]-1
57.1
[{"value": 57.0, "product": "NC1=C(C=C(C=2OCOC21)I)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 57.1, "product": "NC1=C(C=C(C=2OCOC21)I)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3
HOUR
5-Fluoro-1,3-benzodioxol-4-amine (1.1 g, 7.10 mmol), benzyltrimethylammonium dichloroiodate (2.7 g, 7.76 mmol) and calcium carbonate (0.92 g, 9.2 mmol) in a mixture of dichloromethane (10 ml) and methanol (5 ml) were stirred at room temperature for 3 hr. The mixture was filtered through Celite and then evaporated to a ...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ccc2c(c1)OCO2
c1ccc2c(c1)OCO2
c1ccc2c(c1)OCO2
Other
ClCCl.CO
null
3
Nc1c(F)ccc2c1OCO2>ClCCl.CO>Nc1c(F)cc(I)c2c1OCO2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-2d15ad3c88c042edbba2f2e018d07877
COCC#Cc1cc(F)cc2c1OC(N)O2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCS(=O)(=O)CC1>>COCC#Cc1cc(F)c(Nc2ncnc3cc(OCCCN4CCS(=O)(=O)CC4)c(OC)cc23)c2c1OCO2
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCS(CC1)(=O)=O.FC1=CC2=C(OC(O2)N)C(=C1)C#CCOC.C[Si](C)(C)[N-][Si](C)(C)C.[Na+]>>O=S1(CCN(CC1)CCCOC1=C(C=C2C(=NC=NC2=C1)NC1=C(C=C(C=2OCOC21)C#CCOC)F)OC)=O
[CH3:1][O:2][CH2:3][C:4]#[C:5][c:6]1[cH:7][c:8]([F:9])[cH:10][c:36]2[c:37]1[O:38][CH:39]([NH2:11])[O:40]2.Cl[c:12]1[n:13][cH:14][n:15][c:16]2[cH:17][c:18]([O:19][CH2:20][CH2:21][CH2:22][N:23]3[CH2:24][CH2:25][S:26](=[O:27])(=[O:28])[CH2:29][CH2:30]3)[c:31]([O:32][CH3:33])[cH:34][c:35]12>>[CH3:1][O:2][CH2:3][C:4]#[C:5][...
COCC#Cc1cc(F)cc2c1OC(N)O2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCS(=O)(=O)CC1
COCC#Cc1cc(F)c(Nc2ncnc3cc(OCCCN4CCS(=O)(=O)CC4)c(OC)cc23)c2c1OCO2
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
OtherReaction
8d8d958541a668a8e4a7b9c38e8c19a2d704e8170d6ab4859e11cd0ae2f5309f
073f62a3818e3c589c6cf905d1f7b64adb426c91fc96c232669654b3fe83ad5b
O=S1(=O)CCN(CCCOc2ccc3c(Nc4cccc5c4OCO5)ncnc3c2)CC1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[F;D1;H0:9]-[c:10](:[c:11]):[cH;D2;+0:12]:[c:13]1:[c:14]-[#8:15]-[CH;D3;+0:16](-[NH2;D1;+0:17])-[#8:18]-1>>[F;D1;H0:9]-[c:10](:[c:11]):[c;H0;D3;+0:12](-[NH;D2;+0:17]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:13]1:[c:14]...
87
[{"value": 87.0, "product": "O=S1(CCN(CC1)CCCOC1=C(C=C2C(=NC=NC2=C1)NC1=C(C=C(C=2OCOC21)C#CCOC)F)OC)=O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
This was prepared using the method described in example 4 using 4-chloro-7-[3-(1,1-dioxidothiomorpholin-4-yl)propoxy]-6-methoxyquinazoline (150 mg, 0.39 mmol), 5-fluoro-7-(3-methoxyprop-1-yn-1-yl)-1,3-benzodioxolamine (91 mg, 0.41 mmol) and a solution of sodium bis(trimethylsilyl)amide (1.0M in THF, 0.82 ml) in DMF (2....
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Ether.Ether.Primary amine
Ether.Ether.Secondary amine
c1ccc2c(c1)OCO2.c1ccc2ncncc2c1
c1ccc2ncncc2c1.c1ccc2c(c1)OCO2
c1ccc2ncncc2c1.C1CSCC[NH]1.c1ccc2c(c1)OCO2
HCl
CN(C)C=O
null
null
COCC#Cc1cc(F)cc2c1OC(N)O2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCS(=O)(=O)CC1>CN(C)C=O>COCC#Cc1cc(F)c(Nc2ncnc3cc(OCCCN4CCS(=O)(=O)CC4)c(OC)cc23)c2c1OCO2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-91553e00759a490f9aba0023e4e56409
COCC#Cc1cc(F)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(C(C)=O)CC1>>COCC#Cc1cc(F)c(Nc2ncnc3cc(OCCCN4CCN(C(C)=O)CC4)c(OC)cc23)c2c1OCO2
C(C)(=O)N1CCN(CC1)CCCOC1=C(C=C2C(=NC=NC2=C1)Cl)OC.FC1=C(C2=C(OCO2)C(=C1)C#CCOC)N.C[Si](C)(C)[N-][Si](C)(C)C.[Na+]>>C(C)(=O)N1CCN(CC1)CCCOC1=C(C=C2C(=NC=NC2=C1)NC1=C(C=C(C=2OCOC21)C#CCOC)F)OC
[CH3:1][O:2][CH2:3][C:4]#[C:5][c:6]1[cH:7][c:8]([F:9])[c:10]([NH2:11])[c:37]2[c:38]1[O:39][CH2:40][O:41]2.Cl[c:12]1[n:13][cH:14][n:15][c:16]2[cH:17][c:18]([O:19][CH2:20][CH2:21][CH2:22][N:23]3[CH2:24][CH2:25][N:26]([C:27]([CH3:28])=[O:29])[CH2:30][CH2:31]3)[c:32]([O:33][CH3:34])[cH:35][c:36]12>>[CH3:1][O:2][CH2:3][C:4]...
COCC#Cc1cc(F)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(C(C)=O)CC1
COCC#Cc1cc(F)c(Nc2ncnc3cc(OCCCN4CCN(C(C)=O)CC4)c(OC)cc23)c2c1OCO2
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
94bd1d6b149f0eabeae34be7987089f25636bc079a6d701a568fe61e8bfdb7f3
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1cc(Nc2ncnc3cc(OCCCN4CCNCC4)ccc23)c2c(c1)OCO2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#8:9]-[c:10]:[c:11](-[NH2;D1;+0:12]):[c:13]>>[#8:9]-[c:10]:[c:11](-[NH;D2;+0:12]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:13]
72
[{"value": 72.0, "product": "C(C)(=O)N1CCN(CC1)CCCOC1=C(C=C2C(=NC=NC2=C1)NC1=C(C=C(C=2OCOC21)C#CCOC)F)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 71.6, "product": "C(C)(=O)N1CCN(CC1)CCCOC1=C(C=C2C(=NC=NC2=C1)NC1=C(C=C(C=2OCOC21)C#CCOC)F)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
This was prepared using the, method described in the example 4 using 7-[3-(4-acetylpiperazin-1-yl)propoxy]-4-chloro-6-methoxyquinazoline (150 mg, 0.40 mmol), 5-fluoro-7-(3-methoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-amine (97 mg, 0.43 mmol) and a solution of sodium bis(trimethylsilyl)amide (1.0M in THF, 0.83 ml) in DMF (2...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.C1C[NH]CC[NH]1.c1ccc2c(c1)OCO2
HCl
CN(C)C=O
null
null
COCC#Cc1cc(F)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(C(C)=O)CC1>CN(C)C=O>COCC#Cc1cc(F)c(Nc2ncnc3cc(OCCCN4CCN(C(C)=O)CC4)c(OC)cc23)c2c1OCO2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-9dda3c0e7a704bc8979c8831a11755f0
COCCC#Cc1cc(Cl)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1>>COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCOCC4)c(OC)cc23)c2c1OCO2
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1.ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)N.C[Si](C)(C)[N-][Si](C)(C)C.[Na+]>>ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1
[CH3:1][O:2][CH2:3][CH2:4][C:5]#[C:6][c:7]1[cH:8][c:9]([Cl:10])[c:11]([NH2:12])[c:35]2[c:36]1[O:37][CH2:38][O:39]2.Cl[c:13]1[n:14][cH:15][n:16][c:17]2[cH:18][c:19]([O:20][CH2:21][CH2:22][CH2:23][N:24]3[CH2:25][CH2:26][O:27][CH2:28][CH2:29]3)[c:30]([O:31][CH3:32])[cH:33][c:34]12>>[CH3:1][O:2][CH2:3][CH2:4][C:5]#[C:6][c:...
COCCC#Cc1cc(Cl)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1
COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCOCC4)c(OC)cc23)c2c1OCO2
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
94bd1d6b149f0eabeae34be7987089f25636bc079a6d701a568fe61e8bfdb7f3
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1cc(Nc2ncnc3cc(OCCCN4CCOCC4)ccc23)c2c(c1)OCO2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#8:9]-[c:10]:[c:11](-[NH2;D1;+0:12]):[c:13]>>[#8:9]-[c:10]:[c:11](-[NH;D2;+0:12]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:13]
33.3
[{"value": 33.0, "product": "ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 33.3, "product": "ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
This was prepared using the method described in example 4 using 4-chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline (200 mg, 0.59 mmol), 5-chloro-7-(4-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-amine (165 mg, 0.65 mmol) and a solution of sodium bis(trimethylsilyl)amide (1.0M in THF, 1.24 ml) in DMF (3 ml). The crude...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.C1COCC[NH]1.c1ccc2c(c1)OCO2
HCl
CN(C)C=O
null
null
COCCC#Cc1cc(Cl)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1>CN(C)C=O>COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCOCC4)c(OC)cc23)c2c1OCO2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-8bf547caa3d74fd2af9026660ec1851e
COCCC#Cc1cc(F)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1>>COCCC#Cc1cc(F)c(Nc2ncnc3cc(OCCCN4CCOCC4)c(OC)cc23)c2c1OCO2
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1.FC1=C(C2=C(OCO2)C(=C1)C#CCCOC)N.C[Si](C)(C)[N-][Si](C)(C)C.[Na+]>>FC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1
[CH3:1][O:2][CH2:3][CH2:4][C:5]#[C:6][c:7]1[cH:8][c:9]([F:10])[c:11]([NH2:12])[c:35]2[c:36]1[O:37][CH2:38][O:39]2.Cl[c:13]1[n:14][cH:15][n:16][c:17]2[cH:18][c:19]([O:20][CH2:21][CH2:22][CH2:23][N:24]3[CH2:25][CH2:26][O:27][CH2:28][CH2:29]3)[c:30]([O:31][CH3:32])[cH:33][c:34]12>>[CH3:1][O:2][CH2:3][CH2:4][C:5]#[C:6][c:7...
COCCC#Cc1cc(F)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1
COCCC#Cc1cc(F)c(Nc2ncnc3cc(OCCCN4CCOCC4)c(OC)cc23)c2c1OCO2
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
94bd1d6b149f0eabeae34be7987089f25636bc079a6d701a568fe61e8bfdb7f3
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1cc(Nc2ncnc3cc(OCCCN4CCOCC4)ccc23)c2c(c1)OCO2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#8:9]-[c:10]:[c:11](-[NH2;D1;+0:12]):[c:13]>>[#8:9]-[c:10]:[c:11](-[NH;D2;+0:12]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:13]
57.6
[{"value": 57.0, "product": "FC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 57.6, "product": "FC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
This was prepared using the method described in example 4 using 4-chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline (200 mg, 0.59 mmol), 5-fluoro-7-(4-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-amine (154 mg, 0.65 mmol) and a solution of sodium bis(trimethylsilyl)amide (1.0M in THF, 1.25 ml) in DMF (3 ml). The crude...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.C1COCC[NH]1.c1ccc2c(c1)OCO2
HCl
CN(C)C=O
null
null
COCCC#Cc1cc(F)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1>CN(C)C=O>COCCC#Cc1cc(F)c(Nc2ncnc3cc(OCCCN4CCOCC4)c(OC)cc23)c2c1OCO2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-98a753213cf941e28486fe2eb805ad86
CCOCC#Cc1cc(Cl)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1>>CCOCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCOCC4)c(OC)cc23)c2c1OCO2
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1.ClC1=C(C2=C(OCO2)C(=C1)C#CCOCC)N.C[Si](C)(C)[N-][Si](C)(C)C.[Na+]>>ClC1=C(C2=C(OCO2)C(=C1)C#CCOCC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1
[CH3:1][CH2:2][O:3][CH2:4][C:5]#[C:6][c:7]1[cH:8][c:9]([Cl:10])[c:11]([NH2:12])[c:35]2[c:36]1[O:37][CH2:38][O:39]2.Cl[c:13]1[n:14][cH:15][n:16][c:17]2[cH:18][c:19]([O:20][CH2:21][CH2:22][CH2:23][N:24]3[CH2:25][CH2:26][O:27][CH2:28][CH2:29]3)[c:30]([O:31][CH3:32])[cH:33][c:34]12>>[CH3:1][CH2:2][O:3][CH2:4][C:5]#[C:6][c:...
CCOCC#Cc1cc(Cl)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1
CCOCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCOCC4)c(OC)cc23)c2c1OCO2
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
94bd1d6b149f0eabeae34be7987089f25636bc079a6d701a568fe61e8bfdb7f3
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1cc(Nc2ncnc3cc(OCCCN4CCOCC4)ccc23)c2c(c1)OCO2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#8:9]-[c:10]:[c:11](-[NH2;D1;+0:12]):[c:13]>>[#8:9]-[c:10]:[c:11](-[NH;D2;+0:12]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:13]
79.7
[{"value": 79.0, "product": "ClC1=C(C2=C(OCO2)C(=C1)C#CCOCC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 79.7, "product": "ClC1=C(C2=C(OCO2)C(=C1)C#CCOCC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
This was prepared using the method described in example 4 using 4-chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline (200 mg, 0.59 mmol), 5-chloro-7-(3-ethoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-amine (165 mg, 0.65 mmol) and a solution of sodium bis(trimethylsilyl)amide (1.0M in THF, 1.24 ml) in DMF (3 ml). The crude...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.C1COCC[NH]1.c1ccc2c(c1)OCO2
HCl
CN(C)C=O
null
null
CCOCC#Cc1cc(Cl)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1>CN(C)C=O>CCOCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCOCC4)c(OC)cc23)c2c1OCO2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-7463d5ac6fc3463687627bcc22aaefab
COCCOCC#Cc1cc(Cl)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1>>COCCOCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCOCC4)c(OC)cc23)c2c1OCO2
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1.ClC1=C(C2=C(OCO2)C(=C1)C#CCOCCOC)N.C[Si](C)(C)[N-][Si](C)(C)C.[Na+]>>ClC1=C(C2=C(OCO2)C(=C1)C#CCOCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1
[CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][C:7]#[C:8][c:9]1[cH:10][c:11]([Cl:12])[c:13]([NH2:14])[c:37]2[c:38]1[O:39][CH2:40][O:41]2.Cl[c:15]1[n:16][cH:17][n:18][c:19]2[cH:20][c:21]([O:22][CH2:23][CH2:24][CH2:25][N:26]3[CH2:27][CH2:28][O:29][CH2:30][CH2:31]3)[c:32]([O:33][CH3:34])[cH:35][c:36]12>>[CH3:1][O:2][CH2:3][CH2:4]...
COCCOCC#Cc1cc(Cl)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1
COCCOCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCOCC4)c(OC)cc23)c2c1OCO2
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
94bd1d6b149f0eabeae34be7987089f25636bc079a6d701a568fe61e8bfdb7f3
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1cc(Nc2ncnc3cc(OCCCN4CCOCC4)ccc23)c2c(c1)OCO2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#8:9]-[c:10]:[c:11](-[NH2;D1;+0:12]):[c:13]>>[#8:9]-[c:10]:[c:11](-[NH;D2;+0:12]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:13]
77.6
[{"value": 77.0, "product": "ClC1=C(C2=C(OCO2)C(=C1)C#CCOCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 77.6, "product": "ClC1=C(C2=C(OCO2)C(=C1)C#CCOCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
This was prepared using the method described in example 4 using 4-chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline (200 mg, 0.59 mmol), 5-chloro-7-[3-(2-methoxyethoxy)prop-1-yn-1-yl]-1,3-benzodioxol-4-amine (185 mg, 0.65 mmol) and a solution of sodium bis(trimethylsilyl)amide (1.0M in THF, 1.24 ml) in DMF (3 ml)...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.C1COCC[NH]1.c1ccc2c(c1)OCO2
HCl
CN(C)C=O
null
null
COCCOCC#Cc1cc(Cl)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1>CN(C)C=O>COCCOCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCOCC4)c(OC)cc23)c2c1OCO2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-da4f073e48274596bac6afd0de47976e
C#CCOCCOC.Nc1c(Cl)cc(I)c2c1OCO2>>COCCOCC#Cc1cc(Cl)c(N)c2c1OCO2
ClC1=C(C2=C(OCO2)C(=C1)I)N.COCCOCC#C.C(C)(C)NC(C)C>>ClC1=C(C2=C(OCO2)C(=C1)C#CCOCCOC)N
[CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][C:7]#[CH:8].I[c:9]1[cH:10][c:11]([Cl:12])[c:13]([NH2:14])[c:15]2[c:16]1[O:17][CH2:18][O:19]2>>[CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][C:7]#[C:8][c:9]1[cH:10][c:11]([Cl:12])[c:13]([NH2:14])[c:15]2[c:16]1[O:17][CH2:18][O:19]2
C#CCOCCOC.Nc1c(Cl)cc(I)c2c1OCO2
COCCOCC#Cc1cc(Cl)c(N)c2c1OCO2
null
[Pd](Cl)Cl.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.[Cu]I
C(C)(=O)OCC
C-C Coupling
Sonogashira alkyne_aryl halide
4fe05dd9f4e06ca437f6fd540183d70cbf88cbb037b34a93217c201e7139cd32
305eca0fd2975da49e7f69e4edfb9dc1cbce82513954bc5a73be3289e70e5f76
c1ccc2c(c1)OCO2
I-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]1:[c:5]-[#8:6]-[C:7]-[#8:8]-1.[C:9]-[C:10]#[CH;D1;+0:11]>>[C:9]-[C:10]#[C;H0;D2;+0:11]-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]1:[c:5]-[#8:6]-[C:7]-[#8:8]-1
86
[{"value": 86.0, "product": "ClC1=C(C2=C(OCO2)C(=C1)C#CCOCCOC)N", "details": "PERCENTYIELD", "is_desired": false}, {"value": 85.6, "product": "ClC1=C(C2=C(OCO2)C(=C1)C#CCOCCOC)N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2.5
HOUR
5-Chloro-7-iodo-1,3-benzodioxol-4-amine (1.0 g, 3.36 mmol) and 3-(2-methoxyethoxy)prop-1-yne (766 mg, 6.72 mmol) in ethyl acetate (12 ml) were cooled in ice-methanol, under an atmosphere of nitrogen, and then treated with bis(triphenylphosphine) palladium(II) dichloride (236 mg, 10 mol %) followed by copper(I) iodide (...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Alkyne
Alkyne
c1ccc2c(c1)OCO2
c1ccc2c(c1)OCO2
c1ccc2c(c1)OCO2
HI
[Pd](Cl)Cl.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.[Cu]I.C(C)(=O)OCC
null
2.5
C#CCOCCOC.Nc1c(Cl)cc(I)c2c1OCO2>[Pd](Cl)Cl.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.[Cu]I.C(C)(=O)OCC>COCCOCC#Cc1cc(Cl)c(N)c2c1OCO2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-7964d59c0c7649a787bd8ee1409aa931
CC(C)OCC#Cc1cc(Cl)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1>>COc1cc2c(Nc3c(Cl)cc(C#CCOC(C)C)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1.ClC1=C(C2=C(OCO2)C(=C1)C#CCOC(C)C)N.C[Si](C)(C)[N-][Si](C)(C)C.[Na+]>>ClC1=C(C2=C(OCO2)C(=C1)C#CCOC(C)C)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1
[NH2:7][c:8]1[c:9]([Cl:10])[cH:11][c:12]([C:13]#[C:14][CH2:15][O:16][CH:17]([CH3:18])[CH3:19])[c:20]2[c:21]1[O:22][CH2:23][O:24]2.Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:30]([O:31][CH2:32][CH2:33][CH2:34][N:35]3[CH2:36][CH2:37][O:38][CH2:39][CH2:40]3)[cH:29][c:28]2[n:27][cH:26][n:25]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[...
CC(C)OCC#Cc1cc(Cl)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1
COc1cc2c(Nc3c(Cl)cc(C#CCOC(C)C)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
94bd1d6b149f0eabeae34be7987089f25636bc079a6d701a568fe61e8bfdb7f3
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1cc(Nc2ncnc3cc(OCCCN4CCOCC4)ccc23)c2c(c1)OCO2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#8:9]-[c:10]:[c:11](-[NH2;D1;+0:12]):[c:13]>>[#8:9]-[c:10]:[c:11](-[NH;D2;+0:12]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:13]
66.1
[{"value": 66.0, "product": "ClC1=C(C2=C(OCO2)C(=C1)C#CCOC(C)C)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 66.1, "product": "ClC1=C(C2=C(OCO2)C(=C1)C#CCOC(C)C)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
This was prepared using the method described in example 4 using 4-chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline (200 mg, 0.59 mmol), 5-chloro-7-(3-isopropoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-amine (174 mg, 0.65 mmol) and a solution of sodium bis(trimethylsilyl)amide (1.0M in THF, 1.24 ml) in DMF (3 ml). The c...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2c(c1)OCO2.c1ccc2ncncc2c1.C1COCC[NH]1
HCl
CN(C)C=O
null
null
CC(C)OCC#Cc1cc(Cl)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1>CN(C)C=O>COc1cc2c(Nc3c(Cl)cc(C#CCOC(C)C)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-e90b30b417e14c0da8c9a12b575ea345
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Nc1c(Cl)cc(C#CCOCC2CC2)c2c1OCO2>>COc1cc2c(Nc3c(Cl)cc(C#CCOCC4CC4)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1.ClC1=C(C2=C(OCO2)C(=C1)C#CCOCC1CC1)N.C[Si](C)(C)[N-][Si](C)(C)C.[Na+]>>ClC1=C(C2=C(OCO2)C(=C1)C#CCOCC1CC1)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:31]([O:32][CH2:33][CH2:34][CH2:35][N:36]3[CH2:37][CH2:38][O:39][CH2:40][CH2:41]3)[cH:30][c:29]2[n:28][cH:27][n:26]1.[NH2:7][c:8]1[c:9]([Cl:10])[cH:11][c:12]([C:13]#[C:14][CH2:15][O:16][CH2:17][CH:18]2[CH2:19][CH2:20]2)[c:21]2[c:22]1[O:23][CH2:24][O:25]2>>[CH3:1][O:2][c:3]1[cH:4...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Nc1c(Cl)cc(C#CCOCC2CC2)c2c1OCO2
COc1cc2c(Nc3c(Cl)cc(C#CCOCC4CC4)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
94bd1d6b149f0eabeae34be7987089f25636bc079a6d701a568fe61e8bfdb7f3
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
C(#Cc1ccc(Nc2ncnc3cc(OCCCN4CCOCC4)ccc23)c2c1OCO2)COCC1CC1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#8:9]-[c:10]:[c:11](-[NH2;D1;+0:12]):[c:13]>>[#8:9]-[c:10]:[c:11](-[NH;D2;+0:12]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:13]
72
[{"value": 72.0, "product": "ClC1=C(C2=C(OCO2)C(=C1)C#CCOCC1CC1)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 72.0, "product": "ClC1=C(C2=C(OCO2)C(=C1)C#CCOCC1CC1)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
This was prepared using the method described in example 4 using 4-chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline (200 mg, 0.59 mmol), 5-chloro-7-[3-(cyclopropylmethoxy)prop-1-yn-1-yl]-1,3-benzodioxol-4-amine (182 mg, 0.65 mmol) and a solution of sodium bis(trimethylsilyl)amide (1.0M in THF, 1.24 ml) in DMF (3 ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncncc2c1
c1ccc2ncncc2c1
C1CC1.c1ccc2c(c1)OCO2.c1ccc2ncncc2c1.C1COCC[NH]1
HCl
CN(C)C=O
null
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Nc1c(Cl)cc(C#CCOCC2CC2)c2c1OCO2>CN(C)C=O>COc1cc2c(Nc3c(Cl)cc(C#CCOCC4CC4)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ff6d403082bb4c9caf5ce5a3e20fbcf0
C#CCOCC1CC1.Nc1c(Cl)cc(I)c2c1OCO2>>Nc1c(Cl)cc(C#CCOCC2CC2)c2c1OCO2
ClC1=C(C2=C(OCO2)C(=C1)I)N.C(C#C)OCC1CC1.C(C)(C)NC(C)C>>ClC1=C(C2=C(OCO2)C(=C1)C#CCOCC1CC1)N
[CH:7]#[C:8][CH2:9][O:10][CH2:11][CH:12]1[CH2:13][CH2:14]1.I[c:6]1[cH:5][c:3]([Cl:4])[c:2]([NH2:1])[c:16]2[c:15]1[O:19][CH2:18][O:17]2>>[NH2:1][c:2]1[c:3]([Cl:4])[cH:5][c:6]([C:7]#[C:8][CH2:9][O:10][CH2:11][CH:12]2[CH2:13][CH2:14]2)[c:15]2[c:16]1[O:17][CH2:18][O:19]2
C#CCOCC1CC1.Nc1c(Cl)cc(I)c2c1OCO2
Nc1c(Cl)cc(C#CCOCC2CC2)c2c1OCO2
null
[Pd](Cl)Cl.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.[Cu]I
C(C)(=O)OCC
C-C Coupling
Sonogashira alkyne_aryl halide
4fe05dd9f4e06ca437f6fd540183d70cbf88cbb037b34a93217c201e7139cd32
305eca0fd2975da49e7f69e4edfb9dc1cbce82513954bc5a73be3289e70e5f76
C(#Cc1cccc2c1OCO2)COCC1CC1
I-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]1:[c:5]-[#8:6]-[C:7]-[#8:8]-1.[C:9]-[C:10]#[CH;D1;+0:11]>>[C:9]-[C:10]#[C;H0;D2;+0:11]-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]1:[c:5]-[#8:6]-[C:7]-[#8:8]-1
90.4
[{"value": 90.0, "product": "ClC1=C(C2=C(OCO2)C(=C1)C#CCOCC1CC1)N", "details": "PERCENTYIELD", "is_desired": false}, {"value": 90.4, "product": "ClC1=C(C2=C(OCO2)C(=C1)C#CCOCC1CC1)N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
4
HOUR
5-Chloro-7-iodo-1,3-benzodioxol-4-amine (1.0 g, 3.36 mmol) and [(prop-2-yn-1-yloxy)methyl]cyclopropane (739 mg, 6.72 mmol) in ethyl acetate (12 ml) were cooled in ice-methanol, under an atmosphere of nitrogen, then treated with bis(triphenylphosphine) palladium(II) dichloride (236 mg, 10 mol %) followed by copper(I) io...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Alkyne
Alkyne
c1ccc2c(c1)OCO2
c1ccc2c(c1)OCO2
C1CC1.c1ccc2c(c1)OCO2
HI
[Pd](Cl)Cl.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.[Cu]I.C(C)(=O)OCC
null
4
C#CCOCC1CC1.Nc1c(Cl)cc(I)c2c1OCO2>[Pd](Cl)Cl.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.[Cu]I.C(C)(=O)OCC>Nc1c(Cl)cc(C#CCOCC2CC2)c2c1OCO2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-6491e3b2764442018e042adba2734313
CC(=O)N1CCNCC1.COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCCl)c(OC)cc23)c2c1OCO2>>COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCN(C(C)=O)CC4)c(OC)cc23)c2c1OCO2
ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCCl.C(C)(=O)N1CCNCC1>>C(C)(=O)N1CCN(CC1)CCCOC1=C(C=C2C(=NC=NC2=C1)NC1=C(C=C(C=2OCOC21)C#CCCOC)Cl)OC
[NH:24]1[CH2:25][CH2:26][N:27]([C:28]([CH3:29])=[O:30])[CH2:31][CH2:32]1.Cl[CH2:23][CH2:22][CH2:21][O:20][c:19]1[cH:18][c:17]2[n:16][cH:15][n:14][c:13]([NH:12][c:11]3[c:9]([Cl:10])[cH:8][c:7]([C:6]#[C:5][CH2:4][CH2:3][O:2][CH3:1])[c:39]4[c:38]3[O:42][CH2:41][O:40]4)[c:37]2[cH:36][c:33]1[O:34][CH3:35]>>[CH3:1][O:2][CH2:...
CC(=O)N1CCNCC1.COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCCl)c(OC)cc23)c2c1OCO2
COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCN(C(C)=O)CC4)c(OC)cc23)c2c1OCO2
null
null
COCCO
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
bad6b7d8e43c3debef0c262d60564e43415b41bcee72e526419c8c16be18fec1
523d37155b42c8dc851abeddadebb241cdd90bdf649ba750c35e13c8c752d7b0
c1cc(Nc2ncnc3cc(OCCCN4CCNCC4)ccc23)c2c(c1)OCO2
Cl-[CH2;D2;+0:1]-[C:2]-[C:3].[#7:4]1-[C:5]-[C:6]-[NH;D2;+0:7]-[C:8]-[C:9]-1>>[C:3]-[C:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:7]1-[C:6]-[C:5]-[#7:4]-[C:9]-[C:8]-1
82.6
[{"value": 82.0, "product": "C(C)(=O)N1CCN(CC1)CCCOC1=C(C=C2C(=NC=NC2=C1)NC1=C(C=C(C=2OCOC21)C#CCCOC)Cl)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 82.6, "product": "C(C)(=O)N1CCN(CC1)CCCOC1=C(C=C2C(=NC=NC2=C1)NC1=C(C=C(C=2OCOC21)C#CCCOC)Cl)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": fal...
null
null
null
null
N-[5-Chloro-7-(4-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine (192 mg, 0.38 mmol) and 1-acetylpiperazine (244 mg, 1.9 mmol) in 2-methoxyethanol (4 ml) were stirred and heated at 100° for 12 hr. then quenched in water and extracted with dichloromethane. The combined extract...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amine
Tertiary amine
C1CNCC[NH]1
C1C[NH]CC[NH]1
c1ccc2ncncc2c1.C1C[NH]CC[NH]1.c1ccc2c(c1)OCO2
HCl
COCCO
null
null
CC(=O)N1CCNCC1.COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCCl)c(OC)cc23)c2c1OCO2>COCCO>COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCN(C(C)=O)CC4)c(OC)cc23)c2c1OCO2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-8cc1be49569b4380ba972522b23e8531
COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCCl)c(OC)cc23)c2c1OCO2.OCC1CCNCC1>>COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCC(CO)CC4)c(OC)cc23)c2c1OCO2
ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCCl.N1CCC(CC1)CO>>ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCC(CC1)CO
Cl[CH2:23][CH2:22][CH2:21][O:20][c:19]1[cH:18][c:17]2[n:16][cH:15][n:14][c:13]([NH:12][c:11]3[c:9]([Cl:10])[cH:8][c:7]([C:6]#[C:5][CH2:4][CH2:3][O:2][CH3:1])[c:38]4[c:37]3[O:41][CH2:40][O:39]4)[c:36]2[cH:35][c:32]1[O:33][CH3:34].[NH:24]1[CH2:25][CH2:26][CH:27]([CH2:28][OH:29])[CH2:30][CH2:31]1>>[CH3:1][O:2][CH2:3][CH2:...
COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCCl)c(OC)cc23)c2c1OCO2.OCC1CCNCC1
COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCC(CO)CC4)c(OC)cc23)c2c1OCO2
null
null
COCCO
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
0240b8450ff2c489d02f5f0d90bc953079d7a3ab239d35a03f26392fc248b4ef
523d37155b42c8dc851abeddadebb241cdd90bdf649ba750c35e13c8c752d7b0
c1cc(Nc2ncnc3cc(OCCCN4CCCCC4)ccc23)c2c(c1)OCO2
Cl-[CH2;D2;+0:1]-[C:2]-[C:3].[C:4]-[C:5]-[NH;D2;+0:6]-[C:7]-[C:8]>>[C:3]-[C:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:6](-[C:5]-[C:4])-[C:7]-[C:8]
80
[{"value": 80.0, "product": "ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCC(CC1)CO", "details": "PERCENTYIELD", "is_desired": false}, {"value": 79.9, "product": "ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCC(CC1)CO", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
This was prepared using the method described in example 13 using N-[5-chloro-7-(4-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine (192 mg, 0.38 mmol) and 4-piperidinemethanol (220 mg, 1.9 mmol) in 2-methoxyethanol (4 ml). The crude product was purified by column chromatograph...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amine
Tertiary amine
C1CCNCC1
C1CC[NH]CC1
c1ccc2ncncc2c1.C1CC[NH]CC1.c1ccc2c(c1)OCO2
HCl
COCCO
null
null
COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCCl)c(OC)cc23)c2c1OCO2.OCC1CCNCC1>COCCO>COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCC(CO)CC4)c(OC)cc23)c2c1OCO2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-705e201ed1f54150bae5b932266b0257
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Nc1c(Cl)cc(C#CCNC(=O)N2CCOCC2)c2c1OCO2>>COc1cc2c(Nc3c(Cl)cc(C#CCNC(=O)N4CCOCC4)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1.NC1=C(C=C(C2=C1OCO2)C#CCNC(=O)N2CCOCC2)Cl.C[Si](C)(C)[N-][Si](C)(C)C.[Na+]>>ClC=1C=C(C2=C(OCO2)C1NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1)C#CCNC(=O)N1CCOCC1
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:35]([O:36][CH2:37][CH2:38][CH2:39][N:40]3[CH2:41][CH2:42][O:43][CH2:44][CH2:45]3)[cH:34][c:33]2[n:32][cH:31][n:30]1.[NH2:7][c:8]1[c:9]([Cl:10])[cH:11][c:12]([C:13]#[C:14][CH2:15][NH:16][C:17](=[O:18])[N:19]2[CH2:20][CH2:21][O:22][CH2:23][CH2:24]2)[c:25]2[c:26]1[O:27][CH2:28][O:...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Nc1c(Cl)cc(C#CCNC(=O)N2CCOCC2)c2c1OCO2
COc1cc2c(Nc3c(Cl)cc(C#CCNC(=O)N4CCOCC4)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
94bd1d6b149f0eabeae34be7987089f25636bc079a6d701a568fe61e8bfdb7f3
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
O=C(NCC#Cc1ccc(Nc2ncnc3cc(OCCCN4CCOCC4)ccc23)c2c1OCO2)N1CCOCC1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#8:9]-[c:10]:[c:11](-[NH2;D1;+0:12]):[c:13]>>[#8:9]-[c:10]:[c:11](-[NH;D2;+0:12]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:13]
72.1
[{"value": 72.0, "product": "ClC=1C=C(C2=C(OCO2)C1NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1)C#CCNC(=O)N1CCOCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 72.1, "product": "ClC=1C=C(C2=C(OCO2)C1NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1)C#CCNC(=O)N1CCOCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": f...
null
null
null
null
This was prepared by the method described in example 4 using 4-chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline (200 mg, 0.59 mmol), N-[3-(7-amino-6-chloro-1,3-benzodioxol-4-yl)prop-2-yn-1-yl]morpholine-4-carboxamide (220 mg, 0.65 mmol) and a solution of sodium bis(trimethylsilyl)amide (1.0M in THF, 1.24 ml) in ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncncc2c1
c1ccc2ncncc2c1
C1COCC[NH]1.c1ccc2c(c1)OCO2.c1ccc2ncncc2c1.C1COCC[NH]1
HCl
CN(C)C=O
null
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Nc1c(Cl)cc(C#CCNC(=O)N2CCOCC2)c2c1OCO2>CN(C)C=O>COc1cc2c(Nc3c(Cl)cc(C#CCNC(=O)N4CCOCC4)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-899fcc4891e9410c93e903e7568e6b17
C#CCNC(=O)Oc1ccc([N+](=O)[O-])cc1.C1COCCN1>>C#CCNC(=O)N1CCOCC1
N1CCOCC1.C(C#C)NC(OC1=CC=C(C=C1)[N+](=O)[O-])=O>>C(C#C)NC(=O)N1CCOCC1
O=[N+]([O-])c1ccc(O[C:5]([NH:4][CH2:3][C:2]#[CH:1])=[O:6])cc1.[NH:7]1[CH2:8][CH2:9][O:10][CH2:11][CH2:12]1>>[CH:1]#[C:2][CH2:3][NH:4][C:5](=[O:6])[N:7]1[CH2:8][CH2:9][O:10][CH2:11][CH2:12]1
C#CCNC(=O)Oc1ccc([N+](=O)[O-])cc1.C1COCCN1
C#CCNC(=O)N1CCOCC1
null
null
ClCCl
Acylation
OtherReaction
09154e896c7157b7f9689a575f751f2c9525c214676349059c8525cde3edb5ef
fc4b793bbeca2541e0488e7b2269d1dcbab20357be7785ff606aacdf4ebd8736
C1COCCN1
O=[N+](-[O-])-c1:c:c:c(-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#7:3]-[C:4]-[C:5]#[C;D1;H1:6]):c:c:1.[#8:7]1-[C:8]-[C:9]-[NH;D2;+0:10]-[C:11]-[C:12]-1>>[C;D1;H1:6]#[C:5]-[C:4]-[#7:3]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[N;H0;D3;+0:10]1-[C:9]-[C:8]-[#8:7]-[C:12]-[C:11]-1
92.6
[{"value": 92.0, "product": "C(C#C)NC(=O)N1CCOCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 92.6, "product": "C(C#C)NC(=O)N1CCOCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Morpholine (510 mg, 5.86 mmol) and 4-nitrophenyl prop-2-yn-1-ylcarbamate (800 mg (80% purity), 2.91 mmol) in dichloromethane (10 ml) were stirred at room temperature for 4 hours and then the reaction solution was purified directly by chromatography on silica using ethyl acetate as eluent to give N-prop-2-yn-1-ylmorphol...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Nitro group.Secondary amine
Urea
c1ccccc1.C1COCCN1
C1COCC[NH]1
C1COCC[NH]1
HO-
ClCCl
null
null
C#CCNC(=O)Oc1ccc([N+](=O)[O-])cc1.C1COCCN1>ClCCl>C#CCNC(=O)N1CCOCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-1fcb2972fcc543b897ea9b26af6fc289
C#CCNC(=O)N1CCOCC1.Nc1c(Cl)cc(I)c2c1OCO2>>Nc1c(Cl)cc(C#CCNC(=O)N2CCOCC2)c2c1OCO2
ClC1=C(C2=C(OCO2)C(=C1)I)N.C(C#C)NC(=O)N1CCOCC1.C(C)(C)NC(C)C>>NC1=C(C=C(C2=C1OCO2)C#CCNC(=O)N2CCOCC2)Cl
[CH:7]#[C:8][CH2:9][NH:10][C:11](=[O:12])[N:13]1[CH2:14][CH2:15][O:16][CH2:17][CH2:18]1.I[c:6]1[cH:5][c:3]([Cl:4])[c:2]([NH2:1])[c:20]2[c:19]1[O:23][CH2:22][O:21]2>>[NH2:1][c:2]1[c:3]([Cl:4])[cH:5][c:6]([C:7]#[C:8][CH2:9][NH:10][C:11](=[O:12])[N:13]2[CH2:14][CH2:15][O:16][CH2:17][CH2:18]2)[c:19]2[c:20]1[O:21][CH2:22][O...
C#CCNC(=O)N1CCOCC1.Nc1c(Cl)cc(I)c2c1OCO2
Nc1c(Cl)cc(C#CCNC(=O)N2CCOCC2)c2c1OCO2
null
[Pd](Cl)Cl.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.[Cu]I
C(C)(=O)OCC
C-C Coupling
Sonogashira alkyne_aryl halide
4fe05dd9f4e06ca437f6fd540183d70cbf88cbb037b34a93217c201e7139cd32
305eca0fd2975da49e7f69e4edfb9dc1cbce82513954bc5a73be3289e70e5f76
O=C(NCC#Cc1cccc2c1OCO2)N1CCOCC1
I-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]1:[c:5]-[#8:6]-[C:7]-[#8:8]-1.[C:9]-[C:10]#[CH;D1;+0:11]>>[C:9]-[C:10]#[C;H0;D2;+0:11]-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]1:[c:5]-[#8:6]-[C:7]-[#8:8]-1
78
[{"value": 78.0, "product": "NC1=C(C=C(C2=C1OCO2)C#CCNC(=O)N2CCOCC2)Cl", "details": "PERCENTYIELD", "is_desired": false}, {"value": 77.5, "product": "NC1=C(C=C(C2=C1OCO2)C#CCNC(=O)N2CCOCC2)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3
HOUR
5-Chloro-7-iodo-1,3-benzodioxol-4-amine (600 mg, 2.02 mmol) and N-prop-2-yn-1-ylmorpholine-4-carboxamide (406 mg, 2.42 mmol) in ethyl acetate (10 ml) were cooled in ice-methanol, under an atmosphere of nitrogen, and then treated with bis(triphenylphosphine) palladium(II) dichloride (140 mg, 10 mol %) followed by copper...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Alkyne
Alkyne
c1ccc2c(c1)OCO2
c1ccc2c(c1)OCO2
C1COCC[NH]1.c1ccc2c(c1)OCO2
HI
[Pd](Cl)Cl.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.[Cu]I.C(C)(=O)OCC
null
3
C#CCNC(=O)N1CCOCC1.Nc1c(Cl)cc(I)c2c1OCO2>[Pd](Cl)Cl.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.[Cu]I.C(C)(=O)OCC>Nc1c(Cl)cc(C#CCNC(=O)N2CCOCC2)c2c1OCO2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-f6b67a06e69049aeaa8b8415d1396d21
CN(C)C(=O)NCC#Cc1cc(Cl)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1>>COc1cc2c(Nc3c(Cl)cc(C#CCNC(=O)N(C)C)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1.NC1=C(C=C(C2=C1OCO2)C#CCNC(N(C)C)=O)Cl.C[Si](C)(C)[N-][Si](C)(C)C.[Na+]>>ClC=1C=C(C2=C(OCO2)C1NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1)C#CCNC(N(C)C)=O
[NH2:7][c:8]1[c:9]([Cl:10])[cH:11][c:12]([C:13]#[C:14][CH2:15][NH:16][C:17](=[O:18])[N:19]([CH3:20])[CH3:21])[c:22]2[c:23]1[O:24][CH2:25][O:26]2.Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:32]([O:33][CH2:34][CH2:35][CH2:36][N:37]3[CH2:38][CH2:39][O:40][CH2:41][CH2:42]3)[cH:31][c:30]2[n:29][cH:28][n:27]1>>[CH3:1][O:2][c:3...
CN(C)C(=O)NCC#Cc1cc(Cl)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1
COc1cc2c(Nc3c(Cl)cc(C#CCNC(=O)N(C)C)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
94bd1d6b149f0eabeae34be7987089f25636bc079a6d701a568fe61e8bfdb7f3
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1cc(Nc2ncnc3cc(OCCCN4CCOCC4)ccc23)c2c(c1)OCO2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#8:9]-[c:10]:[c:11](-[NH2;D1;+0:12]):[c:13]>>[#8:9]-[c:10]:[c:11](-[NH;D2;+0:12]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:13]
72.1
[{"value": 72.0, "product": "ClC=1C=C(C2=C(OCO2)C1NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1)C#CCNC(N(C)C)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 72.1, "product": "ClC=1C=C(C2=C(OCO2)C1NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1)C#CCNC(N(C)C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
This was prepared by the method described in example 4 using 4-chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline (200 mg, 0.59 mmol), N′-[3-(7-amino-6-chloro-1,3-benzodioxol-4-yl)prop-2-yn-1-yl]-N,N-dimethylurea (193 mg, 0.65 mmol) and a solution of sodium bis(trimethylsilyl)amide (1.0M in THF, 1.24 ml) in DMF (3...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2c(c1)OCO2.c1ccc2ncncc2c1.C1COCC[NH]1
HCl
CN(C)C=O
null
null
CN(C)C(=O)NCC#Cc1cc(Cl)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1>CN(C)C=O>COc1cc2c(Nc3c(Cl)cc(C#CCNC(=O)N(C)C)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-7148a8bdb98f4432be05718119742861
C#CCNC(=O)Oc1ccc([N+](=O)[O-])cc1.CNC>>C#CCNC(=O)N(C)C
CNC.C(C#C)NC(OC1=CC=C(C=C1)[N+](=O)[O-])=O>>CN(C(=O)NCC#C)C
O=[N+]([O-])c1ccc(O[C:5]([NH:4][CH2:3][C:2]#[CH:1])=[O:6])cc1.[NH:7]([CH3:8])[CH3:9]>>[CH:1]#[C:2][CH2:3][NH:4][C:5](=[O:6])[N:7]([CH3:8])[CH3:9]
C#CCNC(=O)Oc1ccc([N+](=O)[O-])cc1.CNC
C#CCNC(=O)N(C)C
null
null
ClCCl.C1CCOC1
Acylation
OtherReaction
e2d977a702ed644c57a3c6a03e066457d8dc73a51640ae48afb0cf24b6adf835
fc4b793bbeca2541e0488e7b2269d1dcbab20357be7785ff606aacdf4ebd8736
null
O=[N+](-[O-])-c1:c:c:c(-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#7:3]-[C:4]-[C:5]#[C;D1;H1:6]):c:c:1.[C;D1;H3:7]-[NH;D2;+0:8]-[C;D1;H3:9]>>[C;D1;H1:6]#[C:5]-[C:4]-[#7:3]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[N;H0;D3;+0:8](-[C;D1;H3:7])-[C;D1;H3:9]
79
[{"value": 79.0, "product": "CN(C(=O)NCC#C)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Dimethylamine (3.0 ml of a 2.0M solution in THF, 6.0 mmol) and 4-nitrophenyl prop-2-yn-1-ylcarbamate (800 mg (80% purity), 2.91 mmol) in dichloromethane (7 ml) were stirred at room temperature for 4 hr. then the reaction solution purified by chromatography on silica using ethyl acetate as eluent to give N,N-dimethyl-N′...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Nitro group.Secondary amine
Urea
c1ccccc1
null
null
HO-
ClCCl.C1CCOC1
null
null
C#CCNC(=O)Oc1ccc([N+](=O)[O-])cc1.CNC>ClCCl.C1CCOC1>C#CCNC(=O)N(C)C
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-c3e05626616943cbb19396b2669793c4
C#CCNC(=O)N(C)C.NC1(Cl)C=C(I)C2=C(C1)OCO2>>CN(C)C(=O)NCC#Cc1cc(Cl)c(N)c2c1OCO2
ClC1(CC2=C(OCO2)C(=C1)I)N.CN(C(=O)NCC#C)C.C(C)(C)NC(C)C>>NC1=C(C=C(C2=C1OCO2)C#CCNC(N(C)C)=O)Cl
[CH3:1][N:2]([CH3:3])[C:4](=[O:5])[NH:6][CH2:7][C:8]#[CH:9].I[C:10]1=[CH:11][C:12]([Cl:13])([NH2:15])[CH2:14][C:16]2=[C:17]1[O:18][CH2:19][O:20]2>>[CH3:1][N:2]([CH3:3])[C:4](=[O:5])[NH:6][CH2:7][C:8]#[C:9][c:10]1[cH:11][c:12]([Cl:13])[c:14]([NH2:15])[c:16]2[c:17]1[O:18][CH2:19][O:20]2
C#CCNC(=O)N(C)C.NC1(Cl)C=C(I)C2=C(C1)OCO2
CN(C)C(=O)NCC#Cc1cc(Cl)c(N)c2c1OCO2
null
[Pd](Cl)Cl.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.[Cu]I
C(C)(=O)OCC
Aromatic Heterocycle Formation
OtherReaction
2b0a3772e410de844c94c47be109f4ca55f5272dd9761ac50f8feff83778b70b
5db9710764a7249fb1da8c25bd3dc2425f54f0a9f9f87614d5671906363e7f87
c1ccc2c(c1)OCO2
I-[C;H0;D3;+0:1]1=[CH;D2;+0:2]-[C;H0;D4;+0:3](-[Cl;D1;H0:4])(-[NH2;D1;+0:5])-[CH2;D2;+0:6]-[C;H0;D3;+0:7]2=[C;H0;D3;+0:8]-1-[#8:9]-[C:10]-[#8:11]-2.[C:12]-[C:13]#[CH;D1;+0:14]>>[C:12]-[C:13]#[C;H0;D2;+0:14]-[c;H0;D3;+0:1]1:[cH;D2;+0:2]:[c;H0;D3;+0:3](-[Cl;D1;H0:4]):[c;H0;D3;+0:6](-[NH2;D1;+0:5]):[c;H0;D3;+0:7]2:[c;H0;D...
68.4
[{"value": 68.0, "product": "NC1=C(C=C(C2=C1OCO2)C#CCNC(N(C)C)=O)Cl", "details": "PERCENTYIELD", "is_desired": false}, {"value": 68.4, "product": "NC1=C(C=C(C2=C1OCO2)C#CCNC(N(C)C)=O)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3
HOUR
5-Chloro-7-iodo-1,3-benzodioxol-5-amine (682 mg, 2.29 mmol) and N,N-dimethyl-N′-prop-2-yn-1-ylurea (289 mg, 2.29 mmol) in ethyl acetate (10 ml) were cooled in ice-methanol, under an atmosphere of nitrogen, then treated with bis(triphenylphosphine) palladium(II) dichloride (161 mg, 10 mol %) followed by copper(I) iodide...
10.6084/m9.figshare.5104873.v1
null
Tertiary halide.Alkenyl halide.Ether.Ether.Primary amine.Alkyne
Aromatic halide.Ether.Ether.Primary amine.Alkyne
C1=CC2=C(CC1)OCO2
c1ccc2c(c1)OCO2
c1ccc2c(c1)OCO2
HI
[Pd](Cl)Cl.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.[Cu]I.C(C)(=O)OCC
null
3
C#CCNC(=O)N(C)C.NC1(Cl)C=C(I)C2=C(C1)OCO2>[Pd](Cl)Cl.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.[Cu]I.C(C)(=O)OCC>CN(C)C(=O)NCC#Cc1cc(Cl)c(N)c2c1OCO2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-13976471972b4cabb87c6b6d9052a3b2
CNC(=O)NCC#Cc1cc(Cl)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1>>CNC(=O)NCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCOCC4)c(OC)cc23)c2c1OCO2
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1.NC1=C(C=C(C2=C1OCO2)C#CCNC(=O)NC)Cl.C[Si](C)(C)[N-][Si](C)(C)C.[Na+]>>ClC=1C=C(C2=C(OCO2)C1NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1)C#CCNC(=O)NC
[CH3:1][NH:2][C:3](=[O:4])[NH:5][CH2:6][C:7]#[C:8][c:9]1[cH:10][c:11]([Cl:12])[c:13]([NH2:14])[c:37]2[c:38]1[O:39][CH2:40][O:41]2.Cl[c:15]1[n:16][cH:17][n:18][c:19]2[cH:20][c:21]([O:22][CH2:23][CH2:24][CH2:25][N:26]3[CH2:27][CH2:28][O:29][CH2:30][CH2:31]3)[c:32]([O:33][CH3:34])[cH:35][c:36]12>>[CH3:1][NH:2][C:3](=[O:4]...
CNC(=O)NCC#Cc1cc(Cl)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1
CNC(=O)NCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCOCC4)c(OC)cc23)c2c1OCO2
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
94bd1d6b149f0eabeae34be7987089f25636bc079a6d701a568fe61e8bfdb7f3
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1cc(Nc2ncnc3cc(OCCCN4CCOCC4)ccc23)c2c(c1)OCO2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#8:9]-[c:10]:[c:11](-[NH2;D1;+0:12]):[c:13]>>[#8:9]-[c:10]:[c:11](-[NH;D2;+0:12]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:13]
61
[{"value": 61.0, "product": "ClC=1C=C(C2=C(OCO2)C1NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1)C#CCNC(=O)NC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 60.8, "product": "ClC=1C=C(C2=C(OCO2)C1NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1)C#CCNC(=O)NC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
This was prepared by the method described in example 4 using 4-chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline (200 mg, 0.59 mmol), N-[3-(7-amino-6-chloro-1,3-benzodioxol-4-yl)prop-2-yn-1-yl]-N′-methylurea (170 mg, 0.60 mmol) and sodium bis(trimethylsilyl)amide (1.0M in THF, 1.24 ml) in DMF (3 ml). The crude pr...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.C1COCC[NH]1.c1ccc2c(c1)OCO2
HCl
CN(C)C=O
null
null
CNC(=O)NCC#Cc1cc(Cl)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1>CN(C)C=O>CNC(=O)NCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCOCC4)c(OC)cc23)c2c1OCO2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-406e541964b44e17bdd87d62440fc6cf
C#CCNC(=O)NC.Nc1c(Cl)cc(I)c2c1OCO2>>CNC(=O)NCC#Cc1cc(Cl)c(N)c2c1OCO2
ClC1=C(C2=C(OCO2)C(=C1)I)N.CNC(=O)NCC#C.C(C)(C)NC(C)C>>NC1=C(C=C(C2=C1OCO2)C#CCNC(=O)NC)Cl
[CH3:1][NH:2][C:3](=[O:4])[NH:5][CH2:6][C:7]#[CH:8].I[c:9]1[cH:10][c:11]([Cl:12])[c:13]([NH2:14])[c:15]2[c:16]1[O:17][CH2:18][O:19]2>>[CH3:1][NH:2][C:3](=[O:4])[NH:5][CH2:6][C:7]#[C:8][c:9]1[cH:10][c:11]([Cl:12])[c:13]([NH2:14])[c:15]2[c:16]1[O:17][CH2:18][O:19]2
C#CCNC(=O)NC.Nc1c(Cl)cc(I)c2c1OCO2
CNC(=O)NCC#Cc1cc(Cl)c(N)c2c1OCO2
null
[Pd](Cl)Cl.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.[Cu]I
C(C)(=O)OCC
C-C Coupling
Sonogashira alkyne_aryl halide
4fe05dd9f4e06ca437f6fd540183d70cbf88cbb037b34a93217c201e7139cd32
305eca0fd2975da49e7f69e4edfb9dc1cbce82513954bc5a73be3289e70e5f76
c1ccc2c(c1)OCO2
I-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]1:[c:5]-[#8:6]-[C:7]-[#8:8]-1.[C:9]-[C:10]#[CH;D1;+0:11]>>[C:9]-[C:10]#[C;H0;D2;+0:11]-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]1:[c:5]-[#8:6]-[C:7]-[#8:8]-1
37.4
[{"value": 37.0, "product": "NC1=C(C=C(C2=C1OCO2)C#CCNC(=O)NC)Cl", "details": "PERCENTYIELD", "is_desired": false}, {"value": 37.4, "product": "NC1=C(C=C(C2=C1OCO2)C#CCNC(=O)NC)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3
HOUR
5-Chloro-7-iodo-1,3-benzodioxol-4-amine (500 mg, 1.68 mmol) and N-methyl-N′-prop-2-yn-1-ylurea (226 mg, 2.02 mmol) in ethyl acetate (10 ml) were cooled in ice-methanol, under an atmosphere of nitrogen, then treated with bis(triphenylphosphine) palladium(II) dichloride (118 mg, 10 mol %) followed by copper(I) iodide (32...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Alkyne
Alkyne
c1ccc2c(c1)OCO2
c1ccc2c(c1)OCO2
c1ccc2c(c1)OCO2
HI
[Pd](Cl)Cl.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.[Cu]I.C(C)(=O)OCC
null
3
C#CCNC(=O)NC.Nc1c(Cl)cc(I)c2c1OCO2>[Pd](Cl)Cl.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.[Cu]I.C(C)(=O)OCC>CNC(=O)NCC#Cc1cc(Cl)c(N)c2c1OCO2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-2a7a7712521d45429ef2571406f77e4e
CN1CCNCC1.COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCCl)c(OC)cc23)c2c1OCO2>>COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCN(C)CC4)c(OC)cc23)c2c1OCO2
ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCCl.CN1CCNCC1>>ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCN(CC1)C
[NH:24]1[CH2:25][CH2:26][N:27]([CH3:28])[CH2:29][CH2:30]1.Cl[CH2:23][CH2:22][CH2:21][O:20][c:19]1[cH:18][c:17]2[n:16][cH:15][n:14][c:13]([NH:12][c:11]3[c:9]([Cl:10])[cH:8][c:7]([C:6]#[C:5][CH2:4][CH2:3][O:2][CH3:1])[c:37]4[c:36]3[O:40][CH2:39][O:38]4)[c:35]2[cH:34][c:31]1[O:32][CH3:33]>>[CH3:1][O:2][CH2:3][CH2:4][C:5]#...
CN1CCNCC1.COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCCl)c(OC)cc23)c2c1OCO2
COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCN(C)CC4)c(OC)cc23)c2c1OCO2
null
null
COCCO
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
bad6b7d8e43c3debef0c262d60564e43415b41bcee72e526419c8c16be18fec1
523d37155b42c8dc851abeddadebb241cdd90bdf649ba750c35e13c8c752d7b0
c1cc(Nc2ncnc3cc(OCCCN4CCNCC4)ccc23)c2c(c1)OCO2
Cl-[CH2;D2;+0:1]-[C:2]-[C:3].[#7:4]1-[C:5]-[C:6]-[NH;D2;+0:7]-[C:8]-[C:9]-1>>[C:3]-[C:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:7]1-[C:6]-[C:5]-[#7:4]-[C:9]-[C:8]-1
68
[{"value": 68.0, "product": "ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCN(CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 67.8, "product": "ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCN(CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
This was prepared by the method described in example 13 using N-[5-Chloro-7-(4-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine (200 mg, 0.40 mmol) and 1-methylpiperazine (198 mg, 1.98 mmol) in 2-methoxyethanol (4 ml). The crude product was purified by column chromatography on...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amine
Tertiary amine
C1CNCC[NH]1
C1C[NH]CC[NH]1
c1ccc2ncncc2c1.C1C[NH]CC[NH]1.c1ccc2c(c1)OCO2
HCl
COCCO
null
null
CN1CCNCC1.COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCCl)c(OC)cc23)c2c1OCO2>COCCO>COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCN(C)CC4)c(OC)cc23)c2c1OCO2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-7c883de606af43868ac1be7d94f5896d
CNC.COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCCl)c(OC)cc23)c2c1OCO2>>COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN(C)C)c(OC)cc23)c2c1OCO2
ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCCl.CNC>>ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN(C)C
[NH:24]([CH3:25])[CH3:26].Cl[CH2:23][CH2:22][CH2:21][O:20][c:19]1[cH:18][c:17]2[n:16][cH:15][n:14][c:13]([NH:12][c:11]3[c:9]([Cl:10])[cH:8][c:7]([C:6]#[C:5][CH2:4][CH2:3][O:2][CH3:1])[c:33]4[c:32]3[O:36][CH2:35][O:34]4)[c:31]2[cH:30][c:27]1[O:28][CH3:29]>>[CH3:1][O:2][CH2:3][CH2:4][C:5]#[C:6][c:7]1[cH:8][c:9]([Cl:10])[...
CNC.COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCCl)c(OC)cc23)c2c1OCO2
COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN(C)C)c(OC)cc23)c2c1OCO2
null
null
C(C)O
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
6d58cac08ccced0a33ed16fbca180bc12aa011288d6476106d98a7b2cbc3d709
523d37155b42c8dc851abeddadebb241cdd90bdf649ba750c35e13c8c752d7b0
c1cc(Nc2ncnc3ccccc23)c2c(c1)OCO2
Cl-[CH2;D2;+0:1]-[C:2]-[C:3].[C;D1;H3:4]-[NH;D2;+0:5]-[C;D1;H3:6]>>[C:3]-[C:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:5](-[C;D1;H3:4])-[C;D1;H3:6]
77
[{"value": 77.0, "product": "ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN(C)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
N-[5-Chloro-7-(4-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine (200 mg, 0.40 mmol) and dimethylamine (5 ml of a 33% solution in ethanol) were stirred and heated under reflux at 90° for 30 min. before evaporating the solution. A further 5 ml of dimethylamine solution were ad...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amine
Tertiary amine
null
null
c1ccc2ncncc2c1.c1ccc2c(c1)OCO2
HCl
C(C)O
null
null
CNC.COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCCl)c(OC)cc23)c2c1OCO2>C(C)O>COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN(C)C)c(OC)cc23)c2c1OCO2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-4b8ef117e3524324a8958ace0a4d1733
COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCCl)c(OC)cc23)c2c1OCO2.COCCNCCOC>>COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN(CCOC)CCOC)c(OC)cc23)c2c1OCO2
ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCCl.COCCNCCOC>>COCCN(CCCOC1=C(C=C2C(=NC=NC2=C1)NC1=C(C=C(C=2OCOC21)C#CCCOC)Cl)OC)CCOC
Cl[CH2:23][CH2:22][CH2:21][O:20][c:19]1[cH:18][c:17]2[n:16][cH:15][n:14][c:13]([NH:12][c:11]3[c:9]([Cl:10])[cH:8][c:7]([C:6]#[C:5][CH2:4][CH2:3][O:2][CH3:1])[c:39]4[c:38]3[O:42][CH2:41][O:40]4)[c:37]2[cH:36][c:33]1[O:34][CH3:35].[NH:24]([CH2:25][CH2:26][O:27][CH3:28])[CH2:29][CH2:30][O:31][CH3:32]>>[CH3:1][O:2][CH2:3][...
COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCCl)c(OC)cc23)c2c1OCO2.COCCNCCOC
COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN(CCOC)CCOC)c(OC)cc23)c2c1OCO2
null
null
COCCO
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
6d58cac08ccced0a33ed16fbca180bc12aa011288d6476106d98a7b2cbc3d709
523d37155b42c8dc851abeddadebb241cdd90bdf649ba750c35e13c8c752d7b0
c1cc(Nc2ncnc3ccccc23)c2c(c1)OCO2
Cl-[CH2;D2;+0:1]-[C:2]-[C:3].[C:4]-[C:5]-[NH;D2;+0:6]-[C:7]-[C:8]>>[C:3]-[C:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:6](-[C:5]-[C:4])-[C:7]-[C:8]
66
[{"value": 66.0, "product": "COCCN(CCCOC1=C(C=C2C(=NC=NC2=C1)NC1=C(C=C(C=2OCOC21)C#CCCOC)Cl)OC)CCOC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 61.1, "product": "COCCN(CCCOC1=C(C=C2C(=NC=NC2=C1)NC1=C(C=C(C=2OCOC21)C#CCCOC)Cl)OC)CCOC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
This was prepared using the method described in example 13 using N-[5-chloro-7-(4-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine (200 mg, 0.40 mmol) and bis(2-methoxyethyl)amine (264 mg, 1.98 mmol) in 2-methoxyethanol (4 ml). The crude product was purified by column chromato...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amine
Tertiary amine
null
null
c1ccc2ncncc2c1.c1ccc2c(c1)OCO2
HCl
COCCO
null
null
COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCCl)c(OC)cc23)c2c1OCO2.COCCNCCOC>COCCO>COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN(CCOC)CCOC)c(OC)cc23)c2c1OCO2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-386a9cd81d134e42be1324060dfa8a44
COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCCl)c(OC)cc23)c2c1OCO2.O=CN1CCNCC1>>COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCN(C=O)CC4)c(OC)cc23)c2c1OCO2
ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCCl.C(=O)N1CCNCC1>>ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCN(CC1)C=O
Cl[CH2:23][CH2:22][CH2:21][O:20][c:19]1[cH:18][c:17]2[n:16][cH:15][n:14][c:13]([NH:12][c:11]3[c:9]([Cl:10])[cH:8][c:7]([C:6]#[C:5][CH2:4][CH2:3][O:2][CH3:1])[c:38]4[c:37]3[O:41][CH2:40][O:39]4)[c:36]2[cH:35][c:32]1[O:33][CH3:34].[NH:24]1[CH2:25][CH2:26][N:27]([CH:28]=[O:29])[CH2:30][CH2:31]1>>[CH3:1][O:2][CH2:3][CH2:4]...
COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCCl)c(OC)cc23)c2c1OCO2.O=CN1CCNCC1
COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCN(C=O)CC4)c(OC)cc23)c2c1OCO2
null
null
COCCO
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
bad6b7d8e43c3debef0c262d60564e43415b41bcee72e526419c8c16be18fec1
523d37155b42c8dc851abeddadebb241cdd90bdf649ba750c35e13c8c752d7b0
c1cc(Nc2ncnc3cc(OCCCN4CCNCC4)ccc23)c2c(c1)OCO2
Cl-[CH2;D2;+0:1]-[C:2]-[C:3].[#7:4]1-[C:5]-[C:6]-[NH;D2;+0:7]-[C:8]-[C:9]-1>>[C:3]-[C:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:7]1-[C:6]-[C:5]-[#7:4]-[C:9]-[C:8]-1
64
[{"value": 64.0, "product": "ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCN(CC1)C=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 63.6, "product": "ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCN(CC1)C=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
This was prepared using the method described in example 13 using N-[5-chloro-7-(4-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine (200 mg, 0.40 mmol) and 1-formylpiperazine (226 mg, 1.98 mmol) in 2-methoxyethanol (4 ml). The crude product was purified by column chromatography...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amine
Tertiary amine
C1CNCC[NH]1
C1C[NH]CC[NH]1
c1ccc2ncncc2c1.C1C[NH]CC[NH]1.c1ccc2c(c1)OCO2
HCl
COCCO
null
null
COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCCl)c(OC)cc23)c2c1OCO2.O=CN1CCNCC1>COCCO>COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCN(C=O)CC4)c(OC)cc23)c2c1OCO2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-6b83045e29e547b7bec799a4143f6340
COCCC#Cc1cc(Cl)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(CCF)CC1>>COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCN(CCF)CC4)c(OC)cc23)c2c1OCO2
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCN(CC1)CCF.ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)N.C[Si](C)(C)[N-][Si](C)(C)C.[Na+]>>ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCN(CC1)CCF
[CH3:1][O:2][CH2:3][CH2:4][C:5]#[C:6][c:7]1[cH:8][c:9]([Cl:10])[c:11]([NH2:12])[c:38]2[c:39]1[O:40][CH2:41][O:42]2.Cl[c:13]1[n:14][cH:15][n:16][c:17]2[cH:18][c:19]([O:20][CH2:21][CH2:22][CH2:23][N:24]3[CH2:25][CH2:26][N:27]([CH2:28][CH2:29][F:30])[CH2:31][CH2:32]3)[c:33]([O:34][CH3:35])[cH:36][c:37]12>>[CH3:1][O:2][CH2...
COCCC#Cc1cc(Cl)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(CCF)CC1
COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCN(CCF)CC4)c(OC)cc23)c2c1OCO2
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
94bd1d6b149f0eabeae34be7987089f25636bc079a6d701a568fe61e8bfdb7f3
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1cc(Nc2ncnc3cc(OCCCN4CCNCC4)ccc23)c2c(c1)OCO2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#8:9]-[c:10]:[c:11](-[NH2;D1;+0:12]):[c:13]>>[#8:9]-[c:10]:[c:11](-[NH;D2;+0:12]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:13]
60
[{"value": 60.0, "product": "ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCN(CC1)CCF", "details": "PERCENTYIELD", "is_desired": false}, {"value": 59.9, "product": "ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCN(CC1)CCF", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
This was prepared by the method described in example 4 using 4-chloro-7-{3-[4-(2-fluoroethyl)piperazin-1-yl]propoxy}-6-methoxyquinazoline (200 mg, 0.52 mmol), 5-chloro-7-(4-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-amine (146 mg, 0.57 mmol) and sodium bis(trimethylsilyl)amide (1.0M in THF, 1.10 ml) in DMF (3 ml). The cru...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.C1C[NH]CC[NH]1.c1ccc2c(c1)OCO2
HCl
CN(C)C=O
null
null
COCCC#Cc1cc(Cl)c(N)c2c1OCO2.COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(CCF)CC1>CN(C)C=O>COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCN(CCF)CC4)c(OC)cc23)c2c1OCO2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-319d7e7bc5a547a9ad5d7b42063f980a
COc1cc2c(Cl)ncnc2cc1O.OCCCN1CCN(CCF)CC1>>COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(CCF)CC1
CC(C)OC(=O)/N=N/C(=O)OC(C)C.ClC1=NC=NC2=CC(=C(C=C12)OC)O.FCCN1CCN(CC1)CCCO.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.CC(C)(C)OC(=O)/N=N/C(=O)OC(C)(C)C>>ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCN(CC1)CCF
[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([Cl:7])[n:8][cH:9][n:10][c:11]2[cH:12][c:13]1[OH:14].O[CH2:15][CH2:16][CH2:17][N:18]1[CH2:19][CH2:20][N:21]([CH2:22][CH2:23][F:24])[CH2:25][CH2:26]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([Cl:7])[n:8][cH:9][n:10][c:11]2[cH:12][c:13]1[O:14][CH2:15][CH2:16][CH2:17][N:18]1[CH2:19][CH2:20]...
COc1cc2c(Cl)ncnc2cc1O.OCCCN1CCN(CCF)CC1
COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(CCF)CC1
null
null
ClCCl.C1CCOC1
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
86bfb73617450d22f9456ed5ce4d96a73f1f8fc0c016bebae57fda68e2da86a2
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
c1ncc2ccc(OCCCN3CCNCC3)cc2n1
O-[CH2;D2;+0:1]-[C:2]-[C:3].[#7;a:4]:[c:5]:[c:6]:[c:7](-[OH;D1;+0:8]):[c:9]>>[#7;a:4]:[c:5]:[c:6]:[c:7](-[O;H0;D2;+0:8]-[CH2;D2;+0:1]-[C:2]-[C:3]):[c:9]
48
[{"value": 48.0, "product": "ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCN(CC1)CCF", "details": "PERCENTYIELD", "is_desired": false}, {"value": 47.8, "product": "ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCN(CC1)CCF", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
Diisopropylazodicarboxylate (921 mg, 4.56 mmol) was added portionwise, at room temperature, to a stirred suspension of 4-chloro-6-methoxyquinazolin-7-ol (800 mg, 3.80 mmol), 3-[4-(2-fluoroethyl)piperazin-1-yl]propan-1-ol (794 mg, 4.18 mmol) and triphenylphosphine (1.4 g, 5.34 mmol) in THF (20 ml). The reaction was stir...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
null
null
c1ccc2ncncc2c1.C1C[NH]CC[NH]1
HO-
ClCCl.C1CCOC1
null
1
COc1cc2c(Cl)ncnc2cc1O.OCCCN1CCN(CCF)CC1>ClCCl.C1CCOC1>COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(CCF)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3c9b87ce15c1466892dafb25794e12aa
CC(C)(C)OC(=O)N1CCNCC1.FCCBr>>CC(C)(C)OC(=O)N1CCN(CCF)CC1
BrCCF.C([O-])([O-])=O.[K+].[K+].BrCCF.C(C)(C)(C)OC(=O)N1CCNCC1>>C(C)(C)(C)OC(=O)N1CCN(CC1)CCF
[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][CH2:10][NH:11][CH2:15][CH2:16]1.Br[CH2:12][CH2:13][F:14]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][CH2:10][N:11]([CH2:12][CH2:13][F:14])[CH2:15][CH2:16]1
CC(C)(C)OC(=O)N1CCNCC1.FCCBr
CC(C)(C)OC(=O)N1CCN(CCF)CC1
null
null
C(C)#N
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
b703623ddc3b029d4716c15f5414f41773434bcc7e3f3853faf62273596bed77
523d37155b42c8dc851abeddadebb241cdd90bdf649ba750c35e13c8c752d7b0
C1CNCCN1
Br-[CH2;D2;+0:1]-[C:2]-[F;D1;H0:3].[#7:4]1-[C:5]-[C:6]-[NH;D2;+0:7]-[C:8]-[C:9]-1>>[F;D1;H0:3]-[C:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:7]1-[C:8]-[C:9]-[#7:4]-[C:5]-[C:6]-1
57
[{"value": 57.0, "product": "C(C)(C)(C)OC(=O)N1CCN(CC1)CCF", "details": "PERCENTYIELD", "is_desired": false}, {"value": 56.9, "product": "C(C)(C)(C)OC(=O)N1CCN(CC1)CCF", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Potassium carbonate (1.85 g, 13.4 mmol) and 1-bromo-2-fluoroethane (440 μl, 5.9 mmol) were added to a solution of tert-butyl-1-piperazinecarboxylate (1 g, 5.4 mmol) in acetonitrile (12 ml). The reaction mixture was stirred at 65?C for 3.5 hours after which time more 1-bromo-2-fluoroethane (160 μl, 2.1 mmol) was added. ...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amine
Tertiary amine
C1C[NH]CCN1
C1C[NH]CC[NH]1
C1C[NH]CC[NH]1
HBr
C(C)#N
null
null
CC(C)(C)OC(=O)N1CCNCC1.FCCBr>C(C)#N>CC(C)(C)OC(=O)N1CCN(CCF)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-891d5ca82acf457981726b9d1a8dfc7e
CC(C)(C)OC(=O)N1CCN(CCF)CC1.O=C(O)C(F)(F)F>>FCCN1CCNCC1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
FC(C(=O)O)(F)F.C(C)(C)(C)OC(=O)N1CCN(CC1)CCF>>OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.FCCN1CCNCC1
C[C:20](C)(C)[O:19][C:18]([N:7]1[CH2:6][CH2:5][N:4]([CH2:3][CH2:2][F:1])[CH2:9][CH2:8]1)=[O:17].[O:10]=[C:11]([OH:12])[C:13]([F:14])([F:21])[F:23]>>[F:1][CH2:2][CH2:3][N:4]1[CH2:5][CH2:6][NH:7][CH2:8][CH2:9]1.[O:10]=[C:11]([OH:12])[C:13]([F:14])([F:15])[F:16].[O:17]=[C:18]([OH:19])[C:20]([F:21])([F:22])[F:23]
CC(C)(C)OC(=O)N1CCN(CCF)CC1.O=C(O)C(F)(F)F
FCCN1CCNCC1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
null
null
C(Cl)Cl
Functional Group Addition
OtherReaction
63e75daca4f4e76fadebef53e5e157c706073976758fa02f89818055e5e42d40
ae802c34808856bdd715b87a3e9abed66d27e47fe6cd05110d395ff832686723
C1CNCCN1
C-[C;H0;D4;+0:1](-C)(-C)-[O;H0;D2;+0:2]-[C;H0;D3;+0:3](=[O;D1;H0:4])-[N;H0;D3;+0:5]1-[C:6]-[C:7]-[#7:8]-[C:9]-[C:10]-1.[F;D1;H0:11]-[C;H0;D4;+0:12](-[F;H0;D1;+0:13])(-[F;H0;D1;+0:14])-[C:15](=[O;D1;H0:16])-[O;D1;H1:17]>>[#7:8]1-[C:7]-[C:6]-[NH;D2;+0:5]-[C:10]-[C:9]-1.[F;D1;H0:11]-[C;H0;D4;+0:12](-[F;D1;H0:18])(-[F;D1;H...
96
[{"value": 96.0, "product": "OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.FCCN1CCNCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 69.8, "product": "OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.FCCN1CCNCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
40
MINUTE
Trifluoroacetic acid (3 ml, 17.5 mmol) was added to a solution of 4-(2-fluoroethyl)-piperazine-1-carboxylic acid tert-butyl ester (350 mg, 1.5 mmol) in methylene chloride (12 ml). The reaction mixture was stirred at ambient temperature for 40 minutes, before the solvent was evaporated under high vacuum. The residue was...
10.6084/m9.figshare.5104873.v1
null
Trifluoro group.Carbamic ester.Ether.Boc
Trifluoro group.Trifluoro group.Carboxylic acid.Secondary amine
C1C[NH]CC[NH]1
C1C[NH]CCN1
C1C[NH]CCN1
null
C(Cl)Cl
null
0.666667
CC(C)(C)OC(=O)N1CCN(CCF)CC1.O=C(O)C(F)(F)F>C(Cl)Cl>FCCN1CCNCC1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-dadf50e5032348668ad75358a0b5fbde
FCCN1CCNCC1.OCCCBr>>OCCCN1CCN(CCF)CC1
BrCCCO.C([O-])([O-])=O.[K+].[K+].OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.FCCN1CCNCC1>>FCCN1CCN(CC1)CCCO
[NH:5]1[CH2:6][CH2:7][N:8]([CH2:9][CH2:10][F:11])[CH2:12][CH2:13]1.Br[CH2:4][CH2:3][CH2:2][OH:1]>>[OH:1][CH2:2][CH2:3][CH2:4][N:5]1[CH2:6][CH2:7][N:8]([CH2:9][CH2:10][F:11])[CH2:12][CH2:13]1
FCCN1CCNCC1.OCCCBr
OCCCN1CCN(CCF)CC1
null
null
C(C)#N
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
bad6b7d8e43c3debef0c262d60564e43415b41bcee72e526419c8c16be18fec1
523d37155b42c8dc851abeddadebb241cdd90bdf649ba750c35e13c8c752d7b0
C1CNCCN1
Br-[CH2;D2;+0:1]-[C:2]-[C:3].[#7:4]1-[C:5]-[C:6]-[NH;D2;+0:7]-[C:8]-[C:9]-1>>[C:3]-[C:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:7]1-[C:6]-[C:5]-[#7:4]-[C:9]-[C:8]-1
91
[{"value": 91.0, "product": "FCCN1CCN(CC1)CCCO", "details": "PERCENTYIELD", "is_desired": false}, {"value": 90.7, "product": "FCCN1CCN(CC1)CCCO", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
85
CELSIUS
4
HOUR
3-Bromopropan-1-ol (581 mg, 4.18 mmol) and potassium carbonate (2.88 g, 20.9 mmol) were added to a solution of 1-(2-fluoroethyl)-piperazine diTFA salt (1.5 g, 4.18 mmol) in acetonitrile (11 ml). The reaction mixture was stirred at 85° C. for 4 hours and then loaded directly onto a column and eluted with a mixture of me...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amine
Tertiary amine
C1CNCC[NH]1
C1C[NH]CC[NH]1
C1C[NH]CC[NH]1
HBr
C(C)#N
85
4
FCCN1CCNCC1.OCCCBr>C(C)#N>OCCCN1CCN(CCF)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-8f8cfe34e4c84f5096edd5b2bb9fa917
COC1CCNCC1.COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCCl)c(OC)cc23)c2c1OCO2>>COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCC(OC)CC4)c(OC)cc23)c2c1OCO2
ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCCl.COC1CCNCC1>>ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCC(CC1)OC
[NH:24]1[CH2:25][CH2:26][CH:27]([O:28][CH3:29])[CH2:30][CH2:31]1.Cl[CH2:23][CH2:22][CH2:21][O:20][c:19]1[cH:18][c:17]2[n:16][cH:15][n:14][c:13]([NH:12][c:11]3[c:9]([Cl:10])[cH:8][c:7]([C:6]#[C:5][CH2:4][CH2:3][O:2][CH3:1])[c:38]4[c:37]3[O:41][CH2:40][O:39]4)[c:36]2[cH:35][c:32]1[O:33][CH3:34]>>[CH3:1][O:2][CH2:3][CH2:4...
COC1CCNCC1.COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCCl)c(OC)cc23)c2c1OCO2
COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCC(OC)CC4)c(OC)cc23)c2c1OCO2
null
null
COCCO
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
0240b8450ff2c489d02f5f0d90bc953079d7a3ab239d35a03f26392fc248b4ef
523d37155b42c8dc851abeddadebb241cdd90bdf649ba750c35e13c8c752d7b0
c1cc(Nc2ncnc3cc(OCCCN4CCCCC4)ccc23)c2c(c1)OCO2
Cl-[CH2;D2;+0:1]-[C:2]-[C:3].[C:4]-[C:5]-[NH;D2;+0:6]-[C:7]-[C:8]>>[C:3]-[C:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:6](-[C:5]-[C:4])-[C:7]-[C:8]
80
[{"value": 80.0, "product": "ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCC(CC1)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 78.9, "product": "ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCC(CC1)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
This was prepared using the method described in example 13 using N-[5-chloro-7-(4-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine (200 mg, 0.40 mmol) and 4-methoxypiperidine (246 mg, 2.14 mmol) in 2-methoxyethanol (4 ml). The crude product was purified by column chromatograph...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amine
Tertiary amine
C1CCNCC1
C1CC[NH]CC1
c1ccc2ncncc2c1.C1CC[NH]CC1.c1ccc2c(c1)OCO2
HCl
COCCO
null
null
COC1CCNCC1.COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCCl)c(OC)cc23)c2c1OCO2>COCCO>COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCC(OC)CC4)c(OC)cc23)c2c1OCO2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-dfa75bdb4e6845028a04bef467c823d7
CN(C)C(=O)NCC#Cc1cc(Cl)c(N)c2c1OCO2.COc1cc2ncnc(Cl)c2cc1OC>>COc1cc2ncnc(Nc3c(Cl)cc(C#CCNC(=O)N(C)C)c4c3OCO4)c2cc1OC
ClC1=NC=NC2=CC(=C(C=C12)OC)OC.NC1=C(C=C(C2=C1OCO2)C#CCNC(N(C)C)=O)Cl.C[Si](C)(C)[N-][Si](C)(C)C.[Na+]>>ClC=1C=C(C2=C(OCO2)C1NC1=NC=NC2=CC(=C(C=C12)OC)OC)C#CCNC(N(C)C)=O
[NH2:10][c:11]1[c:12]([Cl:13])[cH:14][c:15]([C:16]#[C:17][CH2:18][NH:19][C:20](=[O:21])[N:22]([CH3:23])[CH3:24])[c:25]2[c:26]1[O:27][CH2:28][O:29]2.Cl[c:9]1[n:8][cH:7][n:6][c:5]2[cH:4][c:3]([O:2][CH3:1])[c:32]([O:33][CH3:34])[cH:31][c:30]21>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[n:6][cH:7][n:8][c:9]([NH:10][c:11]3[c:12]([Cl:1...
CN(C)C(=O)NCC#Cc1cc(Cl)c(N)c2c1OCO2.COc1cc2ncnc(Cl)c2cc1OC
COc1cc2ncnc(Nc3c(Cl)cc(C#CCNC(=O)N(C)C)c4c3OCO4)c2cc1OC
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
94bd1d6b149f0eabeae34be7987089f25636bc079a6d701a568fe61e8bfdb7f3
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1cc(Nc2ncnc3ccccc23)c2c(c1)OCO2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#8:9]-[c:10]:[c:11](-[NH2;D1;+0:12]):[c:13]>>[#8:9]-[c:10]:[c:11](-[NH;D2;+0:12]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:13]
77.1
[{"value": 77.0, "product": "ClC=1C=C(C2=C(OCO2)C1NC1=NC=NC2=CC(=C(C=C12)OC)OC)C#CCNC(N(C)C)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 77.1, "product": "ClC=1C=C(C2=C(OCO2)C1NC1=NC=NC2=CC(=C(C=C12)OC)OC)C#CCNC(N(C)C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
This was prepared using the method described in example 4 using 4-chloro-6,7-dimethoxyquinazoline (160 mg, 0.71 mmol), N′-[3-(7-amino-6-chloro-1,3-benzodioxol-4-yl)prop-2-yn-1-yl]-N,N-dimethylurea (232 mg, 0.78 mmol) and sodium bis(trimethylsilyl)amide (1.0M in THF, 1.5 ml) in DMF (3 ml). The crude product was purified...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.c1ccc2c(c1)OCO2
HCl
CN(C)C=O
null
null
CN(C)C(=O)NCC#Cc1cc(Cl)c(N)c2c1OCO2.COc1cc2ncnc(Cl)c2cc1OC>CN(C)C=O>COc1cc2ncnc(Nc3c(Cl)cc(C#CCNC(=O)N(C)C)c4c3OCO4)c2cc1OC
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-343f7a7d141f4104bcc5e97ba57373f9
CN1CCNCC1=O.COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCCl)c(OC)cc23)c2c1OCO2>>COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCN(C)C(=O)C4)c(OC)cc23)c2c1OCO2
ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCCl.CN1C(CNCC1)=O>>ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CC(N(CC1)C)=O
[NH:24]1[CH2:25][CH2:26][N:27]([CH3:28])[C:29](=[O:30])[CH2:31]1.Cl[CH2:23][CH2:22][CH2:21][O:20][c:19]1[cH:18][c:17]2[n:16][cH:15][n:14][c:13]([NH:12][c:11]3[c:9]([Cl:10])[cH:8][c:7]([C:6]#[C:5][CH2:4][CH2:3][O:2][CH3:1])[c:38]4[c:37]3[O:41][CH2:40][O:39]4)[c:36]2[cH:35][c:32]1[O:33][CH3:34]>>[CH3:1][O:2][CH2:3][CH2:4...
CN1CCNCC1=O.COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCCl)c(OC)cc23)c2c1OCO2
COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCN(C)C(=O)C4)c(OC)cc23)c2c1OCO2
null
null
COCCO
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
bad6b7d8e43c3debef0c262d60564e43415b41bcee72e526419c8c16be18fec1
523d37155b42c8dc851abeddadebb241cdd90bdf649ba750c35e13c8c752d7b0
O=C1CN(CCCOc2ccc3c(Nc4cccc5c4OCO5)ncnc3c2)CCN1
Cl-[CH2;D2;+0:1]-[C:2]-[C:3].[C;D1;H3:4]-[#7:5]1-[C:6]-[C:7]-[NH;D2;+0:8]-[C:9]-[C:10]-1=[O;D1;H0:11]>>[C:3]-[C:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:8]1-[C:7]-[C:6]-[#7:5](-[C;D1;H3:4])-[C:10](=[O;D1;H0:11])-[C:9]-1
72
[{"value": 72.0, "product": "ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CC(N(CC1)C)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 71.3, "product": "ClC1=C(C2=C(OCO2)C(=C1)C#CCCOC)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CC(N(CC1)C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false...
null
null
null
null
This was prepared by the method described in example 13 using N-[5-Chloro-7-(4-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine (200 mg, 0.40 mmol) and 1-methylpiperazin-2-one (226 mg, 1.98 mmol) in 2-methoxyethanol (4 ml). The crude product was purified by column chromatograp...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amine
Tertiary amine
C1CNCC[NH]1
C1C[NH]CC[NH]1
c1ccc2ncncc2c1.C1C[NH]CC[NH]1.c1ccc2c(c1)OCO2
HCl
COCCO
null
null
CN1CCNCC1=O.COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCCl)c(OC)cc23)c2c1OCO2>COCCO>COCCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCN(C)C(=O)C4)c(OC)cc23)c2c1OCO2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-e33abe0006cc49f8b4c1967b0f21ae7b
C#CCN1CCCC1=O.COc1cc2c(Nc3c(Cl)cc(I)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1>>COc1cc2c(Nc3c(Cl)cc(C#CCN4CCCC4=O)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1
ClC1=C(C2=C(OCO2)C(=C1)I)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1.C(C#C)N1C(CCC1)=O.C(C)(C)NC(C)C>>ClC=1C=C(C2=C(OCO2)C1NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1)C#CCN1C(CCC1)=O
[CH:13]#[C:14][CH2:15][N:16]1[CH2:17][CH2:18][CH2:19][C:20]1=[O:21].I[c:12]1[cH:11][c:9]([Cl:10])[c:8]([NH:7][c:6]2[c:5]3[cH:4][c:3]([O:2][CH3:1])[c:32]([O:33][CH2:34][CH2:35][CH2:36][N:37]4[CH2:38][CH2:39][O:40][CH2:41][CH2:42]4)[cH:31][c:30]3[n:29][cH:28][n:27]2)[c:23]2[c:22]1[O:26][CH2:25][O:24]2>>[CH3:1][O:2][c:3]1...
C#CCN1CCCC1=O.COc1cc2c(Nc3c(Cl)cc(I)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1
COc1cc2c(Nc3c(Cl)cc(C#CCN4CCCC4=O)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1
null
[Pd](Cl)Cl.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.[Cu]I
C(C)(=O)OCC
C-C Coupling
Sonogashira alkyne_aryl halide
4fe05dd9f4e06ca437f6fd540183d70cbf88cbb037b34a93217c201e7139cd32
305eca0fd2975da49e7f69e4edfb9dc1cbce82513954bc5a73be3289e70e5f76
O=C1CCCN1CC#Cc1ccc(Nc2ncnc3cc(OCCCN4CCOCC4)ccc23)c2c1OCO2
I-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]1:[c:5]-[#8:6]-[C:7]-[#8:8]-1.[C:9]-[C:10]#[CH;D1;+0:11]>>[C:9]-[C:10]#[C;H0;D2;+0:11]-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]1:[c:5]-[#8:6]-[C:7]-[#8:8]-1
40
[{"value": 40.0, "product": "ClC=1C=C(C2=C(OCO2)C1NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1)C#CCN1C(CCC1)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 39.3, "product": "ClC=1C=C(C2=C(OCO2)C1NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1)C#CCN1C(CCC1)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
46
HOUR
N-(5-chloro-7-iodo-1,3-benzodioxol-4-yl)-6-methoxy-7-(3-morpholin-4ylpropoxy)quinazolin-4-amine (250 mg, 0.42 mmol) and 1-prop-2-yn-1-ylpyrrolidin-2-one (103 mg, 0.84 mmol) in ethyl acetate (8 ml) were cooled in ice-methanol, under an atmosphere of nitrogen, then treated with bis(triphenylphosphine) palladium(II) dichl...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Alkyne
Alkyne
c1ccc2c(c1)OCO2
c1ccc2c(c1)OCO2
C1CC[NH]C1.c1ccc2c(c1)OCO2.c1ccc2ncncc2c1.C1COCC[NH]1
HI
[Pd](Cl)Cl.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.[Cu]I.C(C)(=O)OCC
null
46
C#CCN1CCCC1=O.COc1cc2c(Nc3c(Cl)cc(I)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1>[Pd](Cl)Cl.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.[Cu]I.C(C)(=O)OCC>COc1cc2c(Nc3c(Cl)cc(C#CCN4CCCC4=O)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-c7af1041f67345d5aa8f4e3ab4fc4cc9
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Nc1c(Cl)cc(I)c2c1OCO2>>COc1cc2c(Nc3c(Cl)cc(I)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1
C[Si](C)(C)[N-][Si](C)(C)C.[Na+].ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1.ClC1=C(C2=C(OCO2)C(=C1)I)N>>ClC1=C(C2=C(OCO2)C(=C1)I)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:24]([O:25][CH2:26][CH2:27][CH2:28][N:29]3[CH2:30][CH2:31][O:32][CH2:33][CH2:34]3)[cH:23][c:22]2[n:21][cH:20][n:19]1.[NH2:7][c:8]1[c:9]([Cl:10])[cH:11][c:12]([I:13])[c:14]2[c:15]1[O:16][CH2:17][O:18]2>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([NH:7][c:8]3[c:9]([Cl:10])[cH:11][c:12]([...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Nc1c(Cl)cc(I)c2c1OCO2
COc1cc2c(Nc3c(Cl)cc(I)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
94bd1d6b149f0eabeae34be7987089f25636bc079a6d701a568fe61e8bfdb7f3
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1cc(Nc2ncnc3cc(OCCCN4CCOCC4)ccc23)c2c(c1)OCO2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#8:9]-[c:10]:[c:11](-[NH2;D1;+0:12]):[c:13]>>[#8:9]-[c:10]:[c:11](-[NH;D2;+0:12]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:13]
97
[{"value": 97.0, "product": null, "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
N-(5-chloro-7-iodo-1,3-benzodioxol-4-yl)-6-methoxy-7-(3-morpholin-4ylpropoxy)quinazolin-4-amine was prepared using the method described in example 4 using 4-chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline (1.0 g, 2.96 mmol), 5-chloro-7-iodo-1,3-benzodioxol-4-amine (0.97 g, 3.26 mmol) and sodium bis(trimethylsil...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2c(c1)OCO2.c1ccc2ncncc2c1.C1COCC[NH]1
HCl
CN(C)C=O
null
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Nc1c(Cl)cc(I)c2c1OCO2>CN(C)C=O>COc1cc2c(Nc3c(Cl)cc(I)c4c3OCO4)ncnc2cc1OCCCN1CCOCC1