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-c3a75813d0b24864aa4f7cd526efd6aa
ord-62d2192aded34cdfa64452a6022fb411
N#Cc1ccc(CCO)cc1.Oc1cc(O)cc(Cl)c1>>N#Cc1ccc(CCOc2cc(O)cc(Cl)c2)cc1
C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.CCOC(=O)/N=N/C(=O)OCC.ClC1=CC(=CC(=C1)O)O.C(#N)C1=CC=C(C=C1)CCO>>ClC=1C=C(C=C(C1)OCCC1=CC=C(C=C1)C#N)O
[N:1]#[C:2][c:3]1[cH:4][cH:5][c:6]([CH2:7][CH2:8][OH:9])[cH:18][cH:19]1.O[c:10]1[cH:11][c:12]([OH:13])[cH:14][c:15]([Cl:16])[cH:17]1>>[N:1]#[C:2][c:3]1[cH:4][cH:5][c:6]([CH2:7][CH2:8][O:9][c:10]2[cH:11][c:12]([OH:13])[cH:14][c:15]([Cl:16])[cH:17]2)[cH:18][cH:19]1
N#Cc1ccc(CCO)cc1.Oc1cc(O)cc(Cl)c1
N#Cc1ccc(CCOc2cc(O)cc(Cl)c2)cc1
null
null
CCOCC.C(Cl)Cl
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
8915084acbaaf997bf0f89ff5187cb2f89c25dc683fffc57b3391298c8430dd9
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
c1ccc(CCOc2ccccc2)cc1
O-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5].[C:6]-[C:7]-[OH;D1;+0:8]>>[C:6]-[C:7]-[O;H0;D2;+0:8]-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5]
21.3
[{"value": 21.0, "product": "ClC=1C=C(C=C(C1)OCCC1=CC=C(C=C1)C#N)O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 21.3, "product": "ClC=1C=C(C=C(C1)OCCC1=CC=C(C=C1)C#N)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
Triphenylphoshine (32 g; 122 mmol) and diethylazodicarboxylate (19.2 mL; 122 mmol) were dissolved in CH2Cl2 (150 mL). Chloro-3,5-dihydroxybenzene (9.1 g; 63 mmol; from step (i) above) and 2-(4-cyanophenyl)ethanol (9.04 g; 61 mmol) were added and the solution was stirred at room temperature overnight. The mixture was di...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1
HO-
CCOCC.C(Cl)Cl
null
8
N#Cc1ccc(CCO)cc1.Oc1cc(O)cc(Cl)c1>CCOCC.C(Cl)Cl>N#Cc1ccc(CCOc2cc(O)cc(Cl)c2)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-fc3a3854b6594410bd7d1f6b1836866b
N#Cc1ccc(CCOc2cc(O)cc(Cl)c2)cc1.O=S(=O)(Cl)c1ccc(F)cc1Cl>>N#Cc1ccc(CCOc2cc(Cl)cc(OS(=O)(=O)c3ccc(F)cc3Cl)c2)cc1
ClC1=C(C=CC(=C1)F)S(=O)(=O)Cl.ClC=1C=C(C=C(C1)OCCC1=CC=C(C=C1)C#N)O.O>>ClC1=C(C=CC(=C1)F)S(=O)(=O)OC1=CC(=CC(=C1)Cl)OCCC1=CC=C(C=C1)C#N
[N:1]#[C:2][c:3]1[cH:4][cH:5][c:6]([CH2:7][CH2:8][O:9][c:10]2[cH:11][c:12]([Cl:13])[cH:14][c:15]([OH:16])[cH:28]2)[cH:29][cH:30]1.Cl[S:17](=[O:18])(=[O:19])[c:20]1[cH:21][cH:22][c:23]([F:24])[cH:25][c:26]1[Cl:27]>>[N:1]#[C:2][c:3]1[cH:4][cH:5][c:6]([CH2:7][CH2:8][O:9][c:10]2[cH:11][c:12]([Cl:13])[cH:14][c:15]([O:16][S:...
N#Cc1ccc(CCOc2cc(O)cc(Cl)c2)cc1.O=S(=O)(Cl)c1ccc(F)cc1Cl
N#Cc1ccc(CCOc2cc(Cl)cc(OS(=O)(=O)c3ccc(F)cc3Cl)c2)cc1
null
null
N1=CC=CC=C1
Acylation
Formation of Sulfonic Esters
9339e107bef60affc137d23d580808fc37a7625dc676ebb48fe8271cd9670535
7ef9cdb7b67e90f0e8b5d9f8fed73f04903b09cd9fd8ced1da4341e88385cae2
O=S(=O)(Oc1cccc(OCCc2ccccc2)c1)c1ccccc1
Cl-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[c:4](:[c:5]):[c:6].[OH;D1;+0:7]-[c:8](:[c:9]):[c:10]>>[O;D1;H0:2]=[S;H0;D4;+0:1](=[O;D1;H0:3])(-[O;H0;D2;+0:7]-[c:8](:[c:9]):[c:10])-[c:4](:[c:5]):[c:6]
72.1
[{"value": 72.0, "product": "ClC1=C(C=CC(=C1)F)S(=O)(=O)OC1=CC(=CC(=C1)Cl)OCCC1=CC=C(C=C1)C#N", "details": "PERCENTYIELD", "is_desired": false}, {"value": 72.1, "product": "ClC1=C(C=CC(=C1)F)S(=O)(=O)OC1=CC(=CC(=C1)Cl)OCCC1=CC=C(C=C1)C#N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
4
HOUR
2-Chloro-4-fluorobenzenesulfonyl chloride (1.16 g; 5.0 mmol) was added to a cold solution (ice:water temperature) of 3-chloro-5-[2-(4-cyanophenyl)ethoxy]phenol (0.689 g; 2.5 mmol; from step (ii) above) in pyridine (8 mL). The temperature was allowed to rise (slowly) to ambient overnight. The mixture was re-cooled (ice:...
10.6084/m9.figshare.5104873.v1
null
Aromatic alcohol.Sulfonyl halide
Sulfonate
null
null
c1ccccc1.c1ccccc1.c1ccccc1
HCl
N1=CC=CC=C1
null
4
N#Cc1ccc(CCOc2cc(O)cc(Cl)c2)cc1.O=S(=O)(Cl)c1ccc(F)cc1Cl>N1=CC=CC=C1>N#Cc1ccc(CCOc2cc(Cl)cc(OS(=O)(=O)c3ccc(F)cc3Cl)c2)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-aca5d9a5cf0247d095e0826dbde90a3e
Cc1ccc(S(=O)(=O)OCCc2ccc(C#N)cc2)cc1.Nc1ccccc1S>>N#Cc1ccc(CCSc2ccccc2N)cc1
C1(=CC=C(C=C1)S(=O)(=O)OCCC1=CC=C(C=C1)C#N)C.C(=O)([O-])[O-].[K+].[K+].NC1=C(C=CC=C1)S>>NC1=C(C=CC=C1)SCCC1=CC=C(C=C1)C#N
Cc1ccc(S(=O)(=O)O[CH2:8][CH2:7][c:6]2[cH:5][cH:4][c:3]([C:2]#[N:1])[cH:18][cH:17]2)cc1.[SH:9][c:10]1[cH:11][cH:12][cH:13][cH:14][c:15]1[NH2:16]>>[N:1]#[C:2][c:3]1[cH:4][cH:5][c:6]([CH2:7][CH2:8][S:9][c:10]2[cH:11][cH:12][cH:13][cH:14][c:15]2[NH2:16])[cH:17][cH:18]1
Cc1ccc(S(=O)(=O)OCCc2ccc(C#N)cc2)cc1.Nc1ccccc1S
N#Cc1ccc(CCSc2ccccc2N)cc1
null
null
CCO
Heteroatom Alkylation and Arylation
OtherReaction
fa9f9600581ef05dca04b54e63c21080ab3037c0f706082a272f2da0c08c4f32
8d10c46c4c89029273335615fb077055d8239c352e37ee1740069c99de11581b
c1ccc(CCSc2ccccc2)cc1
C-c1:c:c:c(-S(=O)(=O)-O-[CH2;D2;+0:1]-[C:2]-[c:3]):c:c:1.[SH;D1;+0:4]-[c:5](:[c:6]):[c:7]>>[c:6]:[c:5](-[S;H0;D2;+0:4]-[CH2;D2;+0:1]-[C:2]-[c:3]):[c:7]
82.4
[{"value": 78.0, "product": "NC1=C(C=CC=C1)SCCC1=CC=C(C=C1)C#N", "details": "PERCENTYIELD", "is_desired": false}, {"value": 82.4, "product": "NC1=C(C=CC=C1)SCCC1=CC=C(C=C1)C#N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
4-Toluenesulfonic acid, 2-(4-cyanophenyl)ethyl ester (1.9 g; 6.3 mmol; from Example 18(i) above) and K2CO3 (2.0 g) were added to a solution of 2-aminothiophenol (0.875 g; 7.0 mmol) in EtOH (20 mL). The mixture was heated to reflux for 48 hours, cooled, filtered and concentrated in vacuo to an oil which was dissolved in...
10.6084/m9.figshare.5104873.v1
null
Tosylate.Aromatic thiol
Monosulfide
c1ccccc1
null
c1ccccc1.c1ccccc1
TsOH.HO-
CCO
null
null
Cc1ccc(S(=O)(=O)OCCc2ccc(C#N)cc2)cc1.Nc1ccccc1S>CCO>N#Cc1ccc(CCSc2ccccc2N)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-12133860a5c54d39883253623972c7f1
CCC(=O)Nc1ccc(O)cc1C(=O)OC.O=[N+]([O-])c1ccccc1F>>CCC(=O)Nc1ccc(Oc2ccccc2[N+](=O)[O-])cc1C(=O)OC
O.COC(C1=C(C=CC(=C1)O)NC(CC)=O)=O.C([O-])([O-])=O.[K+].[K+].FC1=C(C=CC=C1)[N+](=O)[O-]>>COC(C1=C(C=CC(=C1)OC1=C(C=CC=C1)[N+](=O)[O-])NC(CC)=O)=O
[CH3:1][CH2:2][C:3](=[O:4])[NH:5][c:6]1[cH:7][cH:8][c:9]([OH:10])[cH:20][c:21]1[C:22](=[O:23])[O:24][CH3:25].F[c:11]1[cH:12][cH:13][cH:14][cH:15][c:16]1[N+:17](=[O:18])[O-:19]>>[CH3:1][CH2:2][C:3](=[O:4])[NH:5][c:6]1[cH:7][cH:8][c:9]([O:10][c:11]2[cH:12][cH:13][cH:14][cH:15][c:16]2[N+:17](=[O:18])[O-:19])[cH:20][c:21]1...
CCC(=O)Nc1ccc(O)cc1C(=O)OC.O=[N+]([O-])c1ccccc1F
CCC(=O)Nc1ccc(Oc2ccccc2[N+](=O)[O-])cc1C(=O)OC
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
e4ea1e38252bc3b9c5ec04486386725e6570ab3860d45e337a1d131319bbf0fc
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1ccc(Oc2ccccc2)cc1
F-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[#7;+:5]):[c:6].[OH;D1;+0:7]-[c:8](:[c:9]):[c:10]>>[#7;+:5]-[c:4](:[c:6]):[c;H0;D3;+0:1](-[O;H0;D2;+0:7]-[c:8](:[c:9]):[c:10]):[c:2]:[c:3]
75.6
[{"value": 75.6, "product": "COC(C1=C(C=CC(=C1)OC1=C(C=CC=C1)[N+](=O)[O-])NC(CC)=O)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
A mixture of 5-hydroxy-2-propionylamino-benzoic acid methyl ester (1.0 g, 4.5 mmol) and potassium carbonate (0.62 g, 4.5 mmol) was stirred in DMF (5 mL) for 10 minutes. 2-fluoronitrobenzene (0.63 g, 4.5 mmol) was then added and stirring was continued at room temperature overnight. Water (10 mL) was added and the result...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1
HF
CN(C)C=O
null
8
CCC(=O)Nc1ccc(O)cc1C(=O)OC.O=[N+]([O-])c1ccccc1F>CN(C)C=O>CCC(=O)Nc1ccc(Oc2ccccc2[N+](=O)[O-])cc1C(=O)OC
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-8f276a7881514110b2e1046b912dafe8
CCC(=O)Nc1ccc(Oc2ccccc2N)cc1C(=O)OC.CCC(=O)Nc1ccc(Sc2ccccc2N)cc1C(=O)OC>>CCCNc1ccccc1Oc1ccc(NC(=O)CC)c(C(=O)O)c1
COC(C1=C(C=CC(=C1)OC1=C(C=CC=C1)N)NC(CC)=O)=O.COC(C1=C(C=CC(=C1)SC1=C(C=CC=C1)N)NC(CC)=O)=O>>C(CC)(=O)NC1=C(C(=O)O)C=C(C=C1)OC1=C(C=CC=C1)NCCC
C[O:24][C:22]([c:21]1[c:15]([NH:16][C:17](=[O:18])[CH2:19][CH3:20])[cH:14][cH:13][c:12]([O:11][c:10]2[c:5]([NH2:4])[cH:6][cH:7][cH:8][cH:9]2)[cH:25]1)=[O:23].COC(=O)c1cc(Sc2ccccc2N)ccc1N[C:3](=O)[CH2:2][CH3:1]>>[CH3:1][CH2:2][CH2:3][NH:4][c:5]1[cH:6][cH:7][cH:8][cH:9][c:10]1[O:11][c:12]1[cH:13][cH:14][c:15]([NH:16][C:1...
CCC(=O)Nc1ccc(Oc2ccccc2N)cc1C(=O)OC.CCC(=O)Nc1ccc(Sc2ccccc2N)cc1C(=O)OC
CCCNc1ccccc1Oc1ccc(NC(=O)CC)c(C(=O)O)c1
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
7c9959ece595136903671dbc43e3606173b1661c8592aabffd58c937be899619
eb033e889bc3d0e0de4abfad1774a353af3583b793f1f6246ddd1bf7fd308c55
c1ccc(Oc2ccccc2)cc1
C-O-C(=O)-c1:c:c(-S-c2:c:c:c:c:c:2-N):c:c:c:1-N-[C;H0;D3;+0:1](=O)-[C:2]-[C;D1;H3:3].C-[O;H0;D2;+0:4]-[C:5](=[O;D1;H0:6])-[c:7].[NH2;D1;+0:8]-[c:9](:[c:10]):[c:11]>>[C;D1;H3:3]-[C:2]-[CH2;D2;+0:1]-[NH;D2;+0:8]-[c:9](:[c:10]):[c:11].[O;D1;H0:6]=[C:5](-[OH;D1;+0:4])-[c:7]
null
[]
null
null
null
null
The following compounds were obtained by reacting the intermediate 2-propionylamino-5-(2-amino-phenoxy)-benzoic methyl ester or 5-(2-amino-phenylsulfanyl)-2-propionylamino-benzoic acid methyl ester (EXAMPLE 17) with boronic acids according to EXAMPLE 6 or with aldehydes as described above. Conditions: See reaction.note...
10.6084/m9.figshare.5104873.v1
null
Ester.Ester.Secondary amide.Primary amine.Primary amine.Monosulfide
Carboxylic acid.Secondary amine
c1ccccc1.c1ccccc1
null
c1ccccc1.c1ccccc1
Other
null
null
null
CCC(=O)Nc1ccc(Oc2ccccc2N)cc1C(=O)OC.CCC(=O)Nc1ccc(Sc2ccccc2N)cc1C(=O)OC>>CCCNc1ccccc1Oc1ccc(NC(=O)CC)c(C(=O)O)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-0e623b6bc5f04c73904e0abc285f158f
CCCC(=O)Cl.CCCNc1ccccc1Oc1ccc(NC(=O)CC)c(C(=O)O)c1>>CCCC(=O)Nc1ccccc1Oc1ccc(NC(=O)C2CC2)c(C(=O)O)c1
C(CC)(=O)NC1=C(C(=O)O)C=C(C=C1)OC1=C(C=CC=C1)NCCC.C(CCC)(=O)Cl.C(Cl)Cl>>C(CCC)(=O)NC1=C(OC=2C=CC(=C(C(=O)O)C2)NC(=O)C2CC2)C=CC=C1
Cl[C:4]([CH2:3][CH2:2][CH3:1])=[O:5].CCC[NH:6][c:7]1[cH:8][cH:9][cH:10][cH:11][c:12]1[O:13][c:14]1[cH:15][cH:16][c:17]([NH:18][C:19](=[O:20])[CH2:21][CH3:23])[c:24]([C:25](=[O:26])[OH:27])[cH:28]1>>[CH3:1][CH2:2][CH2:3][C:4](=[O:5])[NH:6][c:7]1[cH:8][cH:9][cH:10][cH:11][c:12]1[O:13][c:14]1[cH:15][cH:16][c:17]([NH:18][C...
CCCC(=O)Cl.CCCNc1ccccc1Oc1ccc(NC(=O)CC)c(C(=O)O)c1
CCCC(=O)Nc1ccccc1Oc1ccc(NC(=O)C2CC2)c(C(=O)O)c1
null
null
null
Acylation
OtherReaction
dfdd11d82189d4bd6e02e360b3ad99b8bc852356d07ad161ee75447d35c43285
6eb461acad9b82d73f63ecd50ffcdfb948c52682e1fcc6482d20f4e00ad2aa6f
O=C(Nc1ccc(Oc2ccccc2)cc1)C1CC1
C-C-C-[NH;D2;+0:1]-[c:2](:[c:3]):[c:4].[CH3;D1;+0:5]-[CH2;D2;+0:6]-[C:7](=[O;D1;H0:8])-[#7:9]-[c:10].Cl-[C;H0;D3;+0:11](=[O;D1;H0:12])-[C:13]-[C:14]>>[C:14]-[C:13]-[C;H0;D3;+0:11](=[O;D1;H0:12])-[NH;D2;+0:1]-[c:2](:[c:3]):[c:4].[O;D1;H0:8]=[C:7](-[#7:9]-[c:10])-[CH;D3;+0:6]1-[C:15]-[CH2;D2;+0:5]-1
31
[{"value": 31.0, "product": "C(CCC)(=O)NC1=C(OC=2C=CC(=C(C(=O)O)C2)NC(=O)C2CC2)C=CC=C1", "details": "PERCENTYIELD", "is_desired": false}]
110
CELSIUS
null
null
A mixture of 5-(2-amino-phenoxy)-2-(cyclopropanecarbonyl-amino)-benzoic acid methyl ester (50.0 mg, 0.153 mmol, prepared according to EXAMPLE 2) and butyryl chloride (23.3 mg, 0.184 mmol) in CH2Cl2 (1.5 mL) was heated in a microwave oven at 110° C. for 10 minutes. The reaction mixture was allowed to reach room temperat...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Secondary amine
Secondary amide
null
C1CC1
c1ccccc1.c1ccccc1.C1CC1
HCl
null
110
null
CCCC(=O)Cl.CCCNc1ccccc1Oc1ccc(NC(=O)CC)c(C(=O)O)c1>>CCCC(=O)Nc1ccccc1Oc1ccc(NC(=O)C2CC2)c(C(=O)O)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-84e606289c9f4648b52ded2ff752b4ed
CCC(=O)Nc1ccc(Oc2ccccc2N)cc1C(=O)OC.O=C=Nc1ccccc1>>CCC(=O)Nc1ccc(Oc2ccccc2NC(=O)Nc2ccccc2)cc1C(=O)O
COC(C1=C(C=CC(=C1)OC1=C(C=CC=C1)N)NC(CC)=O)=O.C1(=CC=CC=C1)N=C=O>>C1(=CC=CC=C1)NC(NC1=C(OC=2C=CC(=C(C(=O)O)C2)NC(CC)=O)C=CC=C1)=O
C[O:31][C:29]([c:28]1[c:6]([NH:5][C:3]([CH2:2][CH3:1])=[O:4])[cH:7][cH:8][c:9]([O:10][c:11]2[cH:12][cH:13][cH:14][cH:15][c:16]2[NH2:17])[cH:27]1)=[O:30].[C:18](=[O:19])=[N:20][c:21]1[cH:22][cH:23][cH:24][cH:25][cH:26]1>>[CH3:1][CH2:2][C:3](=[O:4])[NH:5][c:6]1[cH:7][cH:8][c:9]([O:10][c:11]2[cH:12][cH:13][cH:14][cH:15][c...
CCC(=O)Nc1ccc(Oc2ccccc2N)cc1C(=O)OC.O=C=Nc1ccccc1
CCC(=O)Nc1ccc(Oc2ccccc2NC(=O)Nc2ccccc2)cc1C(=O)O
null
null
C(Cl)Cl
Acylation
OtherReaction
1b1f5d27ed581b17dbaf13aca09e739af76059624bf9c2fd467f15f89c191ed7
836cd3195ff002b70ac993f14127c4a295ae76fd2cc94467565bdc7c17ea4e21
O=C(Nc1ccccc1)Nc1ccccc1Oc1ccccc1
C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4].[NH2;D1;+0:5]-[c:6](:[c:7]):[c:8].[O;D1;H0:9]=[C;H0;D2;+0:10]=[N;H0;D2;+0:11]-[c:12](:[c:13]):[c:14]>>[O;D1;H0:9]=[C;H0;D3;+0:10](-[NH;D2;+0:5]-[c:6](:[c:7]):[c:8])-[NH;D2;+0:11]-[c:12](:[c:13]):[c:14].[O;D1;H0:3]=[C:2](-[OH;D1;+0:1])-[c:4]
80
[{"value": 80.0, "product": "C1(=CC=CC=C1)NC(NC1=C(OC=2C=CC(=C(C(=O)O)C2)NC(CC)=O)C=CC=C1)=O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
A mixture of 2-propionylamino-5-(2-amino-phenoxy)-benzoic acid methyl ester (50.0 mg, 0.153 mmol, prepared as described in EXAMPLE 2) and phenyl isocyanate (21.0 mg, 0.175 mmol) in CH2Cl2 (10 mL) was stirred at room temperature for 2 hours. The solvent was removed by evaporation and the crude ester product was hydrolys...
10.6084/m9.figshare.5104873.v1
null
Ester.Isocyanate.Primary amine
Carboxylic acid.Urea
null
null
c1ccccc1.c1ccccc1.c1ccccc1
Other
C(Cl)Cl
null
2
CCC(=O)Nc1ccc(Oc2ccccc2N)cc1C(=O)OC.O=C=Nc1ccccc1>C(Cl)Cl>CCC(=O)Nc1ccc(Oc2ccccc2NC(=O)Nc2ccccc2)cc1C(=O)O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-0b8091968c0248508f09ffdb2d46031b
FC(F)(F)c1ccccc1CBr.O=C(O)c1cc(O)ccc1NC(=O)C1CC1>>O=C(O)c1cc(OCc2ccccc2C(F)(F)F)ccc1NC(=O)C1CC1
C1(CC1)C(=O)NC1=C(C(=O)O)C=C(C=C1)O.FC(C1=C(CBr)C=CC=C1)(F)F.[OH-].[K+]>>C1(CC1)C(=O)NC1=C(C(=O)O)C=C(C=C1)OCC1=C(C=CC=C1)C(F)(F)F
Br[CH2:8][c:9]1[cH:10][cH:11][cH:12][cH:13][c:14]1[C:15]([F:16])([F:17])[F:18].[O:1]=[C:2]([OH:3])[c:4]1[cH:5][c:6]([OH:7])[cH:19][cH:20][c:21]1[NH:22][C:23](=[O:24])[CH:25]1[CH2:26][CH2:27]1>>[O:1]=[C:2]([OH:3])[c:4]1[cH:5][c:6]([O:7][CH2:8][c:9]2[cH:10][cH:11][cH:12][cH:13][c:14]2[C:15]([F:16])([F:17])[F:18])[cH:19][...
FC(F)(F)c1ccccc1CBr.O=C(O)c1cc(O)ccc1NC(=O)C1CC1
O=C(O)c1cc(OCc2ccccc2C(F)(F)F)ccc1NC(=O)C1CC1
null
null
CC(=O)C
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
O=C(Nc1ccc(OCc2ccccc2)cc1)C1CC1
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]
50
[{"value": 50.0, "product": "C1(CC1)C(=O)NC1=C(C(=O)O)C=C(C=C1)OCC1=C(C=CC=C1)C(F)(F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 49.4, "product": "C1(CC1)C(=O)NC1=C(C(=O)O)C=C(C=C1)OCC1=C(C=CC=C1)C(F)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
4
HOUR
A mixture of 2-(cyclopropanecarbonyl-amino)-5-hydroxy-benzoic acid (7.0 g, 32 mmol) and 2-(trifluoromethyl)-benzyl bromide (9.09 g, 38 mmol) in 0.5 M KOH (158 mL, 79 mmol) and acetone (200 mL) was heated to reflux. After 4 hours, acetone was evaporated and the resulting mixture was diluted with more water and washed wi...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccccc1.c1ccccc1.C1CC1
HBr
CC(=O)C
null
4
FC(F)(F)c1ccccc1CBr.O=C(O)c1cc(O)ccc1NC(=O)C1CC1>CC(=O)C>O=C(O)c1cc(OCc2ccccc2C(F)(F)F)ccc1NC(=O)C1CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-e1a1e104cb264a8a82da99664cd0d420
C=Cc1ccccc1F.CCC(=O)Nc1ccc(Br)cc1C(=O)OC>>CCC(=O)Nc1ccc(/C=C/c2ccccc2F)cc1C(=O)O
FC1=C(C=C)C=CC=C1.COC(C1=C(C=CC(=C1)Br)NC(CC)=O)=O.C([O-])([O-])=O.[K+].[K+].C(CCC)N(CCCC)CCCC.[OH-].[Na+]>>FC1=C(C=CC=C1)/C=C/C=1C=CC(=C(C(=O)O)C1)NC(CC)=O
[CH2:10]=[CH:11][c:12]1[cH:13][cH:14][cH:15][cH:16][c:17]1[F:18].C[O:23][C:21]([c:20]1[c:6]([NH:5][C:3]([CH2:2][CH3:1])=[O:4])[cH:7][cH:8][c:9](Br)[cH:19]1)=[O:22]>>[CH3:1][CH2:2][C:3](=[O:4])[NH:5][c:6]1[cH:7][cH:8][c:9](/[CH:10]=[CH:11]/[c:12]2[cH:13][cH:14][cH:15][cH:16][c:17]2[F:18])[cH:19][c:20]1[C:21](=[O:22])[OH...
C=Cc1ccccc1F.CCC(=O)Nc1ccc(Br)cc1C(=O)OC
CCC(=O)Nc1ccc(/C=C/c2ccccc2F)cc1C(=O)O
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
O.CN(C)C=O
C-C Coupling
OtherReaction
baa255812d3085a2fbde11c9a3bb505607bb1e7be6585b006e36fbd19aacac44
25fe5b093fd8b2d72592e9621976dfa9f08f4d400c17b9b589c6f54a4710e331
C(=C/c1ccccc1)\c1ccccc1
Br-[c;H0;D3;+0:1](:[c:2]:[c:3]-[C:4](=[O;D1;H0:5])-[O;H0;D2;+0:6]-C):[c:7]:[c:8].[CH2;D1;+0:9]=[C:10]-[c:11]>>[O;D1;H0:5]=[C:4](-[OH;D1;+0:6])-[c:3]:[c:2]:[c;H0;D3;+0:1](/[CH;D2;+0:9]=[C:10]/[c:11]):[c:7]:[c:8]
null
[]
150
CELSIUS
18
HOUR
To a mixture of 5-bromo-2-propionylamino-benzoic acid methyl ester (1.0 g, 3.50 mmol), potassium carbonate (532 mg, 3.85 mmol), tri-n-butyl amine (0.917 mL, 3.85 mmol) and PdCl2(PPh3)2 (35 mg, 0.05 mmol) in DMF (20 mL) was added 2-fluoro-styrene (0.50 mL, 4.2 mmol). The reaction mixture was heated to 150° C. and left a...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Ester.Vinyl
Carboxylic acid
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1
HBr
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.O.CN(C)C=O
150
18
C=Cc1ccccc1F.CCC(=O)Nc1ccc(Br)cc1C(=O)OC>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.O.CN(C)C=O>CCC(=O)Nc1ccc(/C=C/c2ccccc2F)cc1C(=O)O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-0c9f48fec2cb482d80d9f2140cec9bbb
COC(=O)c1ccccc1N.OCc1ccccc1>>COC(=O)c1cc(Cc2ccccc2)ccc1N
Cl.C(C=1C(N)=CC=CC1)(=O)OC.C(C1=CC=CC=C1)O.O>>C(C1=CC=CC=C1)C1=CC=C(C(C(=O)OC)=C1)N
[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][cH:15][cH:16][c:17]1[NH2:18].O[CH2:8][c:9]1[cH:10][cH:11][cH:12][cH:13][cH:14]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][c:7]([CH2:8][c:9]2[cH:10][cH:11][cH:12][cH:13][cH:14]2)[cH:15][cH:16][c:17]1[NH2:18]
COC(=O)c1ccccc1N.OCc1ccccc1
COC(=O)c1cc(Cc2ccccc2)ccc1N
null
null
CC=1C=CC(=CC1)C
C-C Coupling
OtherReaction
af88eddf36fc242c9cce4a4d8506a2fbe58640bd518e16ac5d6bb59a1a9d9b61
5086858461038ad8c4c4a388cee61b6d9e9118227e969bc00fcc5a7517669191
c1ccc(Cc2ccccc2)cc1
O-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[#8:5]-[C:6](=[O;D1;H0:7])-[c:8]:[c:9]:[cH;D2;+0:10]:[c:11]:[c:12]>>[#8:5]-[C:6](=[O;D1;H0:7])-[c:8]:[c:9]:[c;H0;D3;+0:10](-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4]):[c:11]:[c:12]
4.4
[{"value": 4.4, "product": "C(C1=CC=CC=C1)C1=CC=C(C(C(=O)OC)=C1)N", "details": "PERCENTYIELD", "is_desired": false}, {"value": 4.4, "product": "C(C1=CC=CC=C1)C1=CC=C(C(C(=O)OC)=C1)N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3
HOUR
Methyl anthranilate (30.9 g; 205 mmols) and benzyl alcohol (4.43 g; 40,9 mmols) were dissolved in 50 mL of p-xylene. Montmorillonite (1.3 g), activated with hydrochloric acid, was added to the reaction mixture, which was then heated to boiling. The water produced during the reaction was collected using a Dean-Starck-ap...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol
null
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1
HO-
CC=1C=CC(=CC1)C
null
3
COC(=O)c1ccccc1N.OCc1ccccc1>CC=1C=CC(=CC1)C>COC(=O)c1cc(Cc2ccccc2)ccc1N
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-3ad511abece24f04a183842d292cd7fa
CCC(=O)Cl.COC(=O)c1cc(Cc2ccccc2)ccc1N>>CCC(=O)Nc1ccc(Cc2ccccc2)cc1C(=O)O
C(C1=CC=CC=C1)C1=CC=C(C(C(=O)OC)=C1)N.C(CC)(=O)Cl.C([O-])(O)=O.[Na+]>>C(C1=CC=CC=C1)C=1C=CC(=C(C(=O)O)C1)NC(CC)=O
Cl[C:3]([CH2:2][CH3:1])=[O:4].C[O:21][C:19]([c:18]1[c:6]([NH2:5])[cH:7][cH:8][c:9]([CH2:10][c:11]2[cH:12][cH:13][cH:14][cH:15][cH:16]2)[cH:17]1)=[O:20]>>[CH3:1][CH2:2][C:3](=[O:4])[NH:5][c:6]1[cH:7][cH:8][c:9]([CH2:10][c:11]2[cH:12][cH:13][cH:14][cH:15][cH:16]2)[cH:17][c:18]1[C:19](=[O:20])[OH:21]
CCC(=O)Cl.COC(=O)c1cc(Cc2ccccc2)ccc1N
CCC(=O)Nc1ccc(Cc2ccccc2)cc1C(=O)O
null
null
C(Cl)(Cl)Cl
Protection
OtherReaction
38d0ee372433fbbe336780b47adc73f08791f5521c108d354eaa542b2747a5b4
88f5d7ff84f4ba180aefa4ce7745e5509dd1a3deb0add33de7fca1d17a38ff92
c1ccc(Cc2ccccc2)cc1
C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]:[c:5](-[NH2;D1;+0:6]):[c:7].Cl-[C;H0;D3;+0:8](=[O;D1;H0:9])-[C:10]-[C;D1;H3:11]>>[C;D1;H3:11]-[C:10]-[C;H0;D3;+0:8](=[O;D1;H0:9])-[NH;D2;+0:6]-[c:5](:[c:7]):[c:4]-[C:2](=[O;D1;H0:3])-[OH;D1;+0:1]
null
[]
60
CELSIUS
18
HOUR
Methyl 5-benzylanthranilate (300 mg; 1.24 mmols) was dissolved in 7 mL of chloroform and propionyl chloride (344 mg; 3.72 mmols) was added and the reaction mixture was left at room temperature for 18 hours. Aqueous saturated sodium bicarbonate (5 mL) was added to the reaction mixture whereafter the organic phase was se...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Ester.Primary amine
Carboxylic acid.Secondary amide
null
null
c1ccccc1.c1ccccc1
HCl
C(Cl)(Cl)Cl
60
18
CCC(=O)Cl.COC(=O)c1cc(Cc2ccccc2)ccc1N>C(Cl)(Cl)Cl>CCC(=O)Nc1ccc(Cc2ccccc2)cc1C(=O)O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-2087ff8c32ec4f379e147c94479483ad
CCC(=O)OC(=O)CC.O=c1[nH]c2ccc(O)cc2c(=O)o1>>CCC(=O)Nc1ccc(O)cc1C(=O)OC
OC1=CC=C2C(C(=O)OC(N2)=O)=C1.C[O-].[Na+].C(CC)(=O)OC(CC)=O>>COC(C1=C(C=CC(=C1)O)NC(CC)=O)=O
CCC(=O)OC(=O)[CH2:2][CH3:1].[c:3]1(=[O:4])[nH:5][c:6]2[cH:7][cH:8][c:9]([OH:10])[cH:11][c:12]2[c:13](=[O:14])[o:15]1>>[CH3:1][CH2:2][C:3](=[O:4])[NH:5][c:6]1[cH:7][cH:8][c:9]([OH:10])[cH:11][c:12]1[C:13](=[O:14])[O:15][CH3:16]
CCC(=O)OC(=O)CC.O=c1[nH]c2ccc(O)cc2c(=O)o1
CCC(=O)Nc1ccc(O)cc1C(=O)OC
null
null
CO
C-C Coupling
OtherReaction
800c25e7540fa530b9df9e0d63d0c4f9b16f474a44597419e10a6e69aa6fa9c3
964ea8aadca46e00cac38224ca36d0cdd5b61a54c25f21006cd47ec67bc0b6e9
c1ccccc1
C-C-C(=O)-O-C(=O)-[CH2;D2;+0:1]-[C;D1;H3:2].[O;D1;H0:3]=[c;H0;D3;+0:4]1:[o;H0;D2;+0:5]:[c;H0;D3;+0:6](=[O;D1;H0:7]):[nH;D2;+0:8]:[c:9](:[c:10]):[c:11]:1:[c:12]>>[C;D1;H3:13]-[O;H0;D2;+0:5]-[C;H0;D3;+0:4](=[O;D1;H0:3])-[c:11](:[c:12]):[c:9](-[NH;D2;+0:8]-[C;H0;D3;+0:6](=[O;D1;H0:7])-[CH2;D2;+0:1]-[C;D1;H3:2]):[c:10]
680
[{"value": 680.0, "product": "COC(C1=C(C=CC(=C1)O)NC(CC)=O)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
5-Hydroxy isatoic anhydride (17.9 g, 0.1 mol) was heated to reflux with sodium methoxide (0.5 g, 0.01 mol) in methanol (600 mL) for 1 h. The reaction mixture was cooled on icebath, propionic anhydride (15.0 g, 0.115 mol) was added and then the mixture was heated to reflux for 0.5 h The mixture was then concentrated und...
10.6084/m9.figshare.5104873.v1
null
Anhydride
Ester.Secondary amide
c1ccc2ncocc2c1
c1ccccc1
c1ccccc1
HO-
CO
null
null
CCC(=O)OC(=O)CC.O=c1[nH]c2ccc(O)cc2c(=O)o1>CO>CCC(=O)Nc1ccc(O)cc1C(=O)OC
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-215d2c327f6d4a1a9bc8cd835e984599
C[O-].O=C(Cl)C1CC1.O=c1[nH]c2ccc([N+](=O)[O-])cc2c(=O)o1>>COC(=O)c1cc([N+](=O)[O-])ccc1NC(=O)C1CC1
O.[N+](=O)([O-])C1=CC=C2C(C(=O)OC(N2)=O)=C1.C[O-].[Na+].C1(CC1)C(=O)Cl>>COC(C1=C(C=CC(=C1)[N+](=O)[O-])NC(=O)C1CC1)=O
[CH3:1][O-:2].Cl[C:15](=[O:16])[CH:17]1[CH2:18][CH2:19]1.O=c1o[c:3](=[O:4])[c:5]2[cH:6][c:7]([N+:8](=[O:9])[O-:10])[cH:11][cH:12][c:13]2[nH:14]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][c:7]([N+:8](=[O:9])[O-:10])[cH:11][cH:12][c:13]1[NH:14][C:15](=[O:16])[CH:17]1[CH2:18][CH2:19]1
C[O-].O=C(Cl)C1CC1.O=c1[nH]c2ccc([N+](=O)[O-])cc2c(=O)o1
COC(=O)c1cc([N+](=O)[O-])ccc1NC(=O)C1CC1
null
null
CO
Acylation
OtherReaction
32775032831a07f6993772d54860229989557a78c48f659e5f73ffbd052e4314
bc4f51e695a72647be11534703474732542179306ee227d4cbe367095aebb2ca
O=C(Nc1ccccc1)C1CC1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]1-[C:4]-[C:5]-1.O=c1:[nH;D2;+0:6]:[c:7](:[c:8]):[c:9](:[c:10]):[c;H0;D3;+0:11](=[O;D1;H0:12]):o:1.[C;D1;H3:13]-[O-;H0;D1:14]>>[C;D1;H3:13]-[O;H0;D2;+0:14]-[C;H0;D3;+0:11](=[O;D1;H0:12])-[c:9](:[c:10]):[c:7](-[NH;D2;+0:6]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]1-[C:4]-[C:5]-1):[c:8]
0.1
[{"value": 0.1, "product": "COC(C1=C(C=CC(=C1)[N+](=O)[O-])NC(=O)C1CC1)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
80
CELSIUS
1
HOUR
5-nitroisatoic anhydride (20.8 g, 0.1 mol) ) was heated to reflux with sodium methoxide (0.5 g, 0.01 mol) in methanol (600 mL). After 1 h, the solvent was evaporated under vacuum and the residue dissolved in 1,2-dichloroethane (400 mL), washed with cold water and dried over MgSO4. Cyclopropanecarbonyl chloride (20.9 g,...
10.6084/m9.figshare.5104873.v1
null
Acyl halide
Ester.Secondary amide
c1ccc2ncocc2c1
c1ccccc1
c1ccccc1.C1CC1
Other
CO
80
1
C[O-].O=C(Cl)C1CC1.O=c1[nH]c2ccc([N+](=O)[O-])cc2c(=O)o1>CO>COC(=O)c1cc([N+](=O)[O-])ccc1NC(=O)C1CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-c4624dff17464e99b1a38f46df62301a
CCC(=O)Nc1ccc(Sc2ccccc2[N+](=O)[O-])cc1C(=O)OC>>CCC(=O)Nc1ccc(Sc2ccccc2N)cc1C(=O)OC
COC(C1=C(C=CC(=C1)SC1=C(C=CC=C1)[N+](=O)[O-])NC(CC)=O)=O.[H][H]>>COC(C1=C(C=CC(=C1)SC1=C(C=CC=C1)N)NC(CC)=O)=O
O=[N+:17]([O-])[c:16]1[c:11]([S:10][c:9]2[cH:8][cH:7][c:6]([NH:5][C:3]([CH2:2][CH3:1])=[O:4])[c:19]([C:20](=[O:21])[O:22][CH3:23])[cH:18]2)[cH:12][cH:13][cH:14][cH:15]1>>[CH3:1][CH2:2][C:3](=[O:4])[NH:5][c:6]1[cH:7][cH:8][c:9]([S:10][c:11]2[cH:12][cH:13][cH:14][cH:15][c:16]2[NH2:17])[cH:18][c:19]1[C:20](=[O:21])[O:22][...
CCC(=O)Nc1ccc(Sc2ccccc2[N+](=O)[O-])cc1C(=O)OC
CCC(=O)Nc1ccc(Sc2ccccc2N)cc1C(=O)OC
null
[Pd]
C(C)(=O)OCC
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
c1ccc(Sc2ccccc2)cc1
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
null
[]
null
null
null
null
A mixture of 5-(2-nitro-phenylsulfanyl)-2-propionylamino-benzoic acid methyl ester (110 mg, 0.31 mmol, prepared according to Sevbo et al. 1976) and palladium-on-charcoal (10%, 25 mg) in ethyl acetate (5 mL) was stirred in an atmosphere of hydrogen (1 atm) at room temperature for 2 hours. The catalyst was filtered off a...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1ccccc1.c1ccccc1
Other
[Pd].C(C)(=O)OCC
null
null
CCC(=O)Nc1ccc(Sc2ccccc2[N+](=O)[O-])cc1C(=O)OC>[Pd].C(C)(=O)OCC>CCC(=O)Nc1ccc(Sc2ccccc2N)cc1C(=O)OC
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-badfb920f6794f76916d9157a13ee71c
CC1(C)C(=O)N(Br)C(=O)N1Br.CCC(=O)Nc1ccc(C)cc1C(=O)OC>>CCC(=O)Nc1ccc(CBr)cc1C(=O)OC
COC(C1=C(C=CC(=C1)C)NC(CC)=O)=O.BrN1C(=O)N(C(=O)C1(C)C)Br>>COC(C1=C(C=CC(=C1)CBr)NC(CC)=O)=O
CC1(C)C(=O)N(Br)C(=O)N1[Br:11].[CH3:1][CH2:2][C:3](=[O:4])[NH:5][c:6]1[cH:7][cH:8][c:9]([CH3:10])[cH:12][c:13]1[C:14](=[O:15])[O:16][CH3:17]>>[CH3:1][CH2:2][C:3](=[O:4])[NH:5][c:6]1[cH:7][cH:8][c:9]([CH2:10][Br:11])[cH:12][c:13]1[C:14](=[O:15])[O:16][CH3:17]
CC1(C)C(=O)N(Br)C(=O)N1Br.CCC(=O)Nc1ccc(C)cc1C(=O)OC
CCC(=O)Nc1ccc(CBr)cc1C(=O)OC
null
C(C1=CC=CC=C1)(=O)OOC(C1=CC=CC=C1)=O
C(Cl)(Cl)Cl.C(Cl)(Cl)(Cl)Cl
Functional Group Interconversion
Bromination
a91473c9fc7adf6b60e0ee6cf76d9fd57c945a06f854d599808c46e63bd1107a
ec61c5bd294ca43b589396f2ba98d7399502293434ea706d257f78fef795027a
c1ccccc1
Br-N1-C(=O)-N(-[Br;H0;D1;+0:1])-C(-C)(-C)-C-1=O.[CH3;D1;+0:2]-[c:3](:[c:4]):[c:5]>>[Br;H0;D1;+0:1]-[CH2;D2;+0:2]-[c:3](:[c:4]):[c:5]
106.6
[{"value": 53.0, "product": "COC(C1=C(C=CC(=C1)CBr)NC(CC)=O)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 106.6, "product": "COC(C1=C(C=CC(=C1)CBr)NC(CC)=O)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
The radical bromination was performed as described by Patil et al. 1989: 5-Methyl-2-propionylamino-benzoic acid methyl ester (8.85 g, 40 mmol) and 1,3-dibromo-5,5-dimethyl hydantoin (DDH) (5,72 g, 20 mmol) in a mixture of CHCl3 (500 mL) and CCl4 (500 mL) was heated to reflux. Every 60 minutes 50 mg of dibenzoyl peroxid...
10.6084/m9.figshare.5104873.v1
null
Urea.Tertiary amide
Primary halide
C1CNCN1
null
c1ccccc1
HBr
C(C1=CC=CC=C1)(=O)OOC(C1=CC=CC=C1)=O.C(Cl)(Cl)Cl.C(Cl)(Cl)(Cl)Cl
null
null
CC1(C)C(=O)N(Br)C(=O)N1Br.CCC(=O)Nc1ccc(C)cc1C(=O)OC>C(C1=CC=CC=C1)(=O)OOC(C1=CC=CC=C1)=O.C(Cl)(Cl)Cl.C(Cl)(Cl)(Cl)Cl>CCC(=O)Nc1ccc(CBr)cc1C(=O)OC
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-f8420a191fe64d6da39e948f3c6427f3
CC(=O)OC(C)=O.C[C@]12C[C@H](c3ccc(OCCCCCSCCCC(F)(F)C(F)(F)F)cc3)[C@H](c3ccc(OC4CCCCO4)cc3)C[C@@H]1CC[C@@H]2O>>CC(=O)O[C@H]1CC[C@H]2C[C@@H](c3ccc(OC4CCCCO4)cc3)[C@@H](c3ccc(OCCCCCSCCCC(F)(F)C(F)(F)F)cc3)C[C@@]21C
O[C@H]1CC[C@H]2C[C@H]([C@H](C[C@]12C)C1=CC=C(C=C1)OCCCCCSCCCC(C(F)(F)F)(F)F)C1=CC=C(C=C1)OC1OCCCC1.C(C)(=O)OC(C)=O.C([O-])(O)=O.[Na+]>>C(C)(=O)O[C@H]1CC[C@H]2C[C@H]([C@H](C[C@]12C)C1=CC=C(C=C1)OCCCCCSCCCC(C(F)(F)F)(F)F)C1=CC=C(C=C1)OC1OCCCC1
CC(=O)O[C:2]([CH3:1])=[O:3].[OH:4][C@H:5]1[CH2:6][CH2:7][C@H:8]2[CH2:9][C@@H:10]([c:11]3[cH:12][cH:13][c:14]([O:15][CH:16]4[CH2:17][CH2:18][CH2:19][CH2:20][O:21]4)[cH:22][cH:23]3)[C@@H:24]([c:25]3[cH:26][cH:27][c:28]([O:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][S:35][CH2:36][CH2:37][CH2:38][C:39]([F:40])([F:41])[C:42...
CC(=O)OC(C)=O.C[C@]12C[C@H](c3ccc(OCCCCCSCCCC(F)(F)C(F)(F)F)cc3)[C@H](c3ccc(OC4CCCCO4)cc3)C[C@@H]1CC[C@@H]2O
CC(=O)O[C@H]1CC[C@H]2C[C@@H](c3ccc(OC4CCCCO4)cc3)[C@@H](c3ccc(OCCCCCSCCCC(F)(F)C(F)(F)F)cc3)C[C@@]21C
null
CN(C1=CC=NC=C1)C
N1=CC=CC=C1
Acylation
Transesterification
a7ad17dd333d7246e42d4632a0a7042db0b0d3b7f2adb7cdb2c46498a22ac4db
c98fee24664998fb42388f3a4804f79d763c5043c4f5565ea3b46913e3a86a6e
c1ccc([C@H]2CC3CCC[C@H]3C[C@H]2c2ccc(OC3CCCCO3)cc2)cc1
C-C(=O)-O-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3].[C:4]-[C:5](-[OH;D1;+0:6])-[C:7]>>[C:4]-[C:5](-[O;H0;D2;+0:6]-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3])-[C:7]
86
[{"value": 86.0, "product": "C(C)(=O)O[C@H]1CC[C@H]2C[C@H]([C@H](C[C@]12C)C1=CC=C(C=C1)OCCCCCSCCCC(C(F)(F)F)(F)F)C1=CC=C(C=C1)OC1OCCCC1", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The solution of 1.43 g (2.51 mmol) of the compound that is presented in Example 2c is reacted analogously to Example 1, and after working-up, a mixture that consists of the title compound is isolated, and (1S,3S,4R,6S,9S)-9-hydroxy-4-[4-(tetrahydropyran-2-yloxy)phenyl]-1-methyl-3-[4-(10,10,11,11,11-pentafluoro-6-thia-u...
10.6084/m9.figshare.5104873.v1
null
Anhydride.Secondary alcohol
Ester
null
null
C1CC[C@@H]2CCC[C@H]2C1.c1ccccc1.C1CCOCC1.c1ccccc1
HO-
CN(C1=CC=NC=C1)C.N1=CC=CC=C1
null
null
CC(=O)OC(C)=O.C[C@]12C[C@H](c3ccc(OCCCCCSCCCC(F)(F)C(F)(F)F)cc3)[C@H](c3ccc(OC4CCCCO4)cc3)C[C@@H]1CC[C@@H]2O>CN(C1=CC=NC=C1)C.N1=CC=CC=C1>CC(=O)O[C@H]1CC[C@H]2C[C@@H](c3ccc(OC4CCCCO4)cc3)[C@@H](c3ccc(OCCCCCSCCCC(F)(F)C(F)(F)F)cc3)C[C@@]21C
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-dcf2571f40d74e4fa4e40efe25cd9928
CC(C)(C)OC(=O)N1C[C@H](O)C[C@H]1C(=O)N1CCC[C@H]1C#N>>CC(C)(C)OC(=O)N1C[C@@H](N)C[C@H]1C(=O)N1CCC[C@H]1C#N
C(C)(C)(C)OC(=O)N1[C@@H](C[C@H](C1)O)C(=O)N1[C@@H](CCC1)C#N.C(C)N(CC)CC>>N[C@H]1C[C@H](N(C1)C(=O)OC(C)(C)C)C(=O)N1[C@@H](CCC1)C#N
O[C@H:10]1[CH2:9][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[C@H:13]([C:14](=[O:15])[N:16]2[CH2:17][CH2:18][CH2:19][C@H:20]2[C:21]#[N:22])[CH2:12]1>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][C@@H:10]([NH2:11])[CH2:12][C@H:13]1[C:14](=[O:15])[N:16]1[CH2:17][CH2:18][CH2:19][C@H:20]1[C:21]#...
CC(C)(C)OC(=O)N1C[C@H](O)C[C@H]1C(=O)N1CCC[C@H]1C#N
CC(C)(C)OC(=O)N1C[C@@H](N)C[C@H]1C(=O)N1CCC[C@H]1C#N
null
null
CN(C)C=O
Functional Group Interconversion
OtherReaction
e4cc4275430598cab66a42f9c2c21b8e5ceb97a0109cfc650cb16b8f9873032e
608b51d94fe5549150a4eeda0c360f1a7d8cad8a20df73f53fb2f5a4d4581c18
O=C([C@@H]1CCCN1)N1CCCC1
O-[C@@H;D3;+0:1]1-[C:2]-[C:3](-[C:4](-[#7:5])=[O;D1;H0:6])-[#7:7](-[C:8](=[O;D1;H0:9])-[#8:10]-[C:11](-[C;D1;H3:12])(-[C;D1;H3:13])-[C;D1;H3:14])-[C:15]-1>>[#7:5]-[C:4](=[O;D1;H0:6])-[C:3]1-[C:2]-[C@H;D3;+0:1](-[N;D1;H2:16])-[C:15]-[#7:7]-1-[C:8](=[O;D1;H0:9])-[#8:10]-[C:11](-[C;D1;H3:12])(-[C;D1;H3:13])-[C;D1;H3:14]
null
[]
null
null
null
null
(S)-1-((2S,4R)-1-tert-Butoxycarbonyl-4-hydroxy-2-pyrrolidinylcarbonyl)-2-cyanopyrrolidine (title compound of Reference Example 2, 60.7 g) and triethylamine (30.1 mL) were dissolved in DMF (300 mL). Methanesulfonyl chloride (16 mL) was added thereto under ice-cooling. After stirring at room temperature for 3 hr, the rea...
10.6084/m9.figshare.5104873.v1
null
Secondary alcohol
Primary amine
C1CC[NH]C1
C1CC[NH]C1
C1CC[NH]C1.C1CC[NH]C1
null
CN(C)C=O
null
null
CC(C)(C)OC(=O)N1C[C@H](O)C[C@H]1C(=O)N1CCC[C@H]1C#N>CN(C)C=O>CC(C)(C)OC(=O)N1C[C@@H](N)C[C@H]1C(=O)N1CCC[C@H]1C#N
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-12c1e64ab7074546a3d625ad998258d9
COC(=O)[C@@H]1C[C@@H](N)CN1C(=O)OC(C)(C)C.Clc1nc2ccccc2o1>>COC(=O)[C@@H]1C[C@@H](Nc2nc3ccccc3o2)CN1C(=O)OC(C)(C)C
O.N[C@@H]1C[C@H](N(C1)C(=O)OC(C)(C)C)C(=O)OC.C(C)N(CC)CC.ClC=1OC2=C(N1)C=CC=C2>>O1C(=NC2=C1C=CC=C2)N[C@@H]2C[C@H](N(C2)C(=O)OC(C)(C)C)C(=O)OC
[CH3:1][O:2][C:3](=[O:4])[C@@H:5]1[CH2:6][C@@H:7]([NH2:8])[CH2:18][N:19]1[C:20](=[O:21])[O:22][C:23]([CH3:24])([CH3:25])[CH3:26].Cl[c:9]1[n:10][c:11]2[cH:12][cH:13][cH:14][cH:15][c:16]2[o:17]1>>[CH3:1][O:2][C:3](=[O:4])[C@@H:5]1[CH2:6][C@@H:7]([NH:8][c:9]2[n:10][c:11]3[cH:12][cH:13][cH:14][cH:15][c:16]3[o:17]2)[CH2:18]...
COC(=O)[C@@H]1C[C@@H](N)CN1C(=O)OC(C)(C)C.Clc1nc2ccccc2o1
COC(=O)[C@@H]1C[C@@H](Nc2nc3ccccc3o2)CN1C(=O)OC(C)(C)C
null
null
O1CCCC1
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation primary amine
56122dec6b9213d311e74462a865e17687f4178b6e2e5d6eb3cc0c5bc48da7a7
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc2oc(N[C@@H]3CCNC3)nc2c1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[c:4]:[#8;a:5]:1.[#7:6]-[C:7]-[C:8](-[NH2;D1;+0:9])-[C:10]>>[#7:6]-[C:7]-[C:8](-[NH;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[c:4]:[#8;a:5]:1)-[C:10]
null
[]
null
null
48
HOUR
Methyl (2S,4R)-4-amino-1-tert-butoxycarbonylpyrrolidine-2-carboxylate [product of Reference Example 4(2), 3.32 g] and triethylamine (1.4 mL) were dissolved in tetrahydrofuran (20 mL). 2-Chlorobenzoxazole (0.86 mL) was added thereto and the mixture was stirred at room temperature for 48 hr. The reaction mixture was adde...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ocnc2c1
c1ccc2ocnc2c1
C1CC[NH]C1.c1ccc2ocnc2c1
HCl
O1CCCC1
null
48
COC(=O)[C@@H]1C[C@@H](N)CN1C(=O)OC(C)(C)C.Clc1nc2ccccc2o1>O1CCCC1>COC(=O)[C@@H]1C[C@@H](Nc2nc3ccccc3o2)CN1C(=O)OC(C)(C)C
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-93270218ce10478a89ccd5f0b8ad94c6
COC(=O)[C@@H]1C[C@H](N)CN1C(=O)OC(C)(C)C.O=C(Cl)c1ccccc1>>COC(=O)[C@@H]1C[C@H](NC(=O)c2ccccc2)CN1C(=O)OC(C)(C)C
O.N[C@H]1C[C@H](N(C1)C(=O)OC(C)(C)C)C(=O)OC.C(C)N(CC)CC.C(C1=CC=CC=C1)(=O)Cl>>C(C1=CC=CC=C1)(=O)N[C@H]1C[C@H](N(C1)C(=O)OC(C)(C)C)C(=O)OC
[CH3:1][O:2][C:3](=[O:4])[C@@H:5]1[CH2:6][C@H:7]([NH2:8])[CH2:17][N:18]1[C:19](=[O:20])[O:21][C:22]([CH3:23])([CH3:24])[CH3:25].Cl[C:9](=[O:10])[c:11]1[cH:12][cH:13][cH:14][cH:15][cH:16]1>>[CH3:1][O:2][C:3](=[O:4])[C@@H:5]1[CH2:6][C@H:7]([NH:8][C:9](=[O:10])[c:11]2[cH:12][cH:13][cH:14][cH:15][cH:16]2)[CH2:17][N:18]1[C:...
COC(=O)[C@@H]1C[C@H](N)CN1C(=O)OC(C)(C)C.O=C(Cl)c1ccccc1
COC(=O)[C@@H]1C[C@H](NC(=O)c2ccccc2)CN1C(=O)OC(C)(C)C
null
null
O1CCCC1
Acylation
Acylation of Nitrogen Nucleophiles by Acyl/Thioacyl/Carbamoyl Halides and Analogs_OS
38143a4d536201990008fd6f2c68e6571a341d1c367481869fbbbe36cb038937
0e6ae078978e324f714e184b4f72826d4e3bf2d9ab22d6e9f73740af687be16f
O=C(N[C@H]1CCNC1)c1ccccc1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[#7:6]-[C:7]-[C:8](-[NH2;D1;+0:9])-[C:10]>>[#7:6]-[C:7]-[C:8](-[NH;D2;+0:9]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5])-[C:10]
null
[]
null
null
1
HOUR
Methyl (2S,4S)-4-amino-1-tert-butoxycarbonylpyrrolidine-2-carboxylate [product of Reference Example 5(3), 2.4 g] and triethylamine (2.0 mL) were dissolved in tetrahydrofuran (20 mL), and benzoyl chloride (1.1 mL) was added thereto. The mixture was stirred for 1 hr. The reaction mixture was added to water and extracted ...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Primary amine
Secondary amide
null
null
C1CC[NH]C1.c1ccccc1
HCl
O1CCCC1
null
1
COC(=O)[C@@H]1C[C@H](N)CN1C(=O)OC(C)(C)C.O=C(Cl)c1ccccc1>O1CCCC1>COC(=O)[C@@H]1C[C@H](NC(=O)c2ccccc2)CN1C(=O)OC(C)(C)C
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-2fdb38059e574bf2a76b53793b763be8
CC(C)(C)OC(=O)N1C[C@H](O)C[C@H]1C(=O)N1CCSC1>>CC(C)(C)OC(=O)N1C[C@@H](N)C[C@H]1C(=O)N1CCSC1
C(C)(C)(C)OC(=O)N1[C@@H](C[C@H](C1)O)C(=O)N1CSCC1.C(C)N(CC)CC>>N[C@H]1C[C@H](N(C1)C(=O)OC(C)(C)C)C(=O)N1CSCC1
O[C@H:10]1[CH2:9][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[C@H:13]([C:14](=[O:15])[N:16]2[CH2:17][CH2:18][S:19][CH2:20]2)[CH2:12]1>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][C@@H:10]([NH2:11])[CH2:12][C@H:13]1[C:14](=[O:15])[N:16]1[CH2:17][CH2:18][S:19][CH2:20]1
CC(C)(C)OC(=O)N1C[C@H](O)C[C@H]1C(=O)N1CCSC1
CC(C)(C)OC(=O)N1C[C@@H](N)C[C@H]1C(=O)N1CCSC1
null
null
ClCCl
Functional Group Interconversion
OtherReaction
e4cc4275430598cab66a42f9c2c21b8e5ceb97a0109cfc650cb16b8f9873032e
608b51d94fe5549150a4eeda0c360f1a7d8cad8a20df73f53fb2f5a4d4581c18
O=C([C@@H]1CCCN1)N1CCSC1
O-[C@@H;D3;+0:1]1-[C:2]-[C:3](-[C:4](-[#7:5])=[O;D1;H0:6])-[#7:7](-[C:8](=[O;D1;H0:9])-[#8:10]-[C:11](-[C;D1;H3:12])(-[C;D1;H3:13])-[C;D1;H3:14])-[C:15]-1>>[#7:5]-[C:4](=[O;D1;H0:6])-[C:3]1-[C:2]-[C@H;D3;+0:1](-[N;D1;H2:16])-[C:15]-[#7:7]-1-[C:8](=[O;D1;H0:9])-[#8:10]-[C:11](-[C;D1;H3:12])(-[C;D1;H3:13])-[C;D1;H3:14]
null
[]
null
null
null
null
3-((2S,4R)-1-tert-Butoxycarbonyl-4-hydroxy-2-pyrrolidinylcarbonyl)-1,3-thiazolidine (title compound of Reference Example 9, 56.3 g) and triethylamine (28.5 mL) were dissolved in dichloromethane (1.0 l), and methanesulfonyl chloride (15.1 mL) was added thereto under ice-cooling. After stirring under ice-cooling for 1 hr...
10.6084/m9.figshare.5104873.v1
null
Secondary alcohol
Primary amine
C1CC[NH]C1
C1CC[NH]C1
C1CC[NH]C1.C1CSC[NH]1
null
ClCCl
null
null
CC(C)(C)OC(=O)N1C[C@H](O)C[C@H]1C(=O)N1CCSC1>ClCCl>CC(C)(C)OC(=O)N1C[C@@H](N)C[C@H]1C(=O)N1CCSC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-27ee47580eff4093893eb1a7d0d256ad
CC(C)(C)OC(=O)N1C[C@@H](N)C[C@H]1C(=O)N1CCC[C@H]1C#N>>Cl.N#C[C@@H]1CCCN1C(=O)[C@@H]1C[C@H](N)CN1
N[C@H]1C[C@H](N(C1)C(=O)OC(C)(C)C)C(=O)N1[C@@H](CCC1)C#N.Cl.O1CCOCC1>>Cl.Cl.N[C@H]1C[C@H](NC1)C(=O)N1[C@@H](CCC1)C#N
CC(C)(C)OC(=O)[N:17]1[C@H:12]([C:10]([N:9]2[C@H:5]([C:4]#[N:3])[CH2:6][CH2:7][CH2:8]2)=[O:11])[CH2:13][C@H:14]([NH2:15])[CH2:16]1>>[ClH:2].[N:3]#[C:4][C@@H:5]1[CH2:6][CH2:7][CH2:8][N:9]1[C:10](=[O:11])[C@@H:12]1[CH2:13][C@H:14]([NH2:15])[CH2:16][NH:17]1
CC(C)(C)OC(=O)N1C[C@@H](N)C[C@H]1C(=O)N1CCC[C@H]1C#N
Cl.N#C[C@@H]1CCCN1C(=O)[C@@H]1C[C@H](N)CN1
null
null
null
Miscellaneous
Boc amine deprotection
f8d276f6195a26b4ed25eb5f7dc89f1f5d8836bc1a35a891d3ddc666caa9552d
c95e79e18f8ea11cf22745e0eab38cab98566b1b63e7d80ee200f4cb4f94f00c
O=C([C@@H]1CCCN1)N1CCCC1
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1]1-[C:2]-[C:3]-[C:4]-[C:5]-1-[C:6](=[O;D1;H0:7])-[#7:8](-[C:9])-[C:10]>>[C:9]-[#7:8](-[C:6](=[O;D1;H0:7])-[C:5]1-[C:4]-[C:3]-[C:2]-[NH;D2;+0:1]-1)-[C:10]
null
[]
null
null
null
null
(S)-1-((2S,4S)-4-Amino-1-tert-butoxycarbonyl-2-pyrrolidinylcarbonyl)-2-cyanopyrrolidine (title compound of Reference Example 3, 308 mg) was dissolved in 4 mol/L hydrochloric acid-1,4-dioxane (1.25 mL), and the mixture was stirred at room temperature for 27 hr. The solvent was evaporated under reduced pressure and tetra...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Secondary amine
C1CC[NH]C1
C1CCNC1
C1CC[NH]C1.C1CCNC1
HO-
null
null
null
CC(C)(C)OC(=O)N1C[C@@H](N)C[C@H]1C(=O)N1CCC[C@H]1C#N>>Cl.N#C[C@@H]1CCCN1C(=O)[C@@H]1C[C@H](N)CN1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-f4aa30a3e9374e00a8e16b40d26689e9
CC(C)(C)OC(=O)N1C[C@H](Nc2ccc(C#N)cn2)C[C@H]1C(=O)O.N#C[C@@H]1CCCN1>>Cl.N#Cc1ccc(N[C@H]2CN[C@H](C(=O)N3CCC[C@H]3C#N)C2)nc1
C(C)(C)(C)OC(=O)N1[C@@H](C[C@H](C1)NC1=NC=C(C=C1)C#N)C(=O)O.Cl.C(#N)[C@H]1NCCC1>>Cl.Cl.C(#N)C=1C=CC(=NC1)N[C@@H]1C[C@H](NC1)C(=O)N1[C@@H](CCC1)C#N
CC(C)(C)OC(=O)[N:12]1[CH2:11][C@H:10]([NH:9][c:8]2[cH:7][cH:6][c:5]([C:4]#[N:3])[cH:25][n:24]2)[CH2:23][C@H:13]1[C:14](O)=[O:15].[NH:16]1[CH2:17][CH2:18][CH2:19][C@H:20]1[C:21]#[N:22]>>[ClH:2].[N:3]#[C:4][c:5]1[cH:6][cH:7][c:8]([NH:9][C@H:10]2[CH2:11][NH:12][C@H:13]([C:14](=[O:15])[N:16]3[CH2:17][CH2:18][CH2:19][C@H:20...
CC(C)(C)OC(=O)N1C[C@H](Nc2ccc(C#N)cn2)C[C@H]1C(=O)O.N#C[C@@H]1CCCN1
Cl.N#Cc1ccc(N[C@H]2CN[C@H](C(=O)N3CCC[C@H]3C#N)C2)nc1
null
null
CN(C)C=O
Acylation
OtherReaction
0f0e880dc075a48f825a869e028ef98e81f3b02c1beed442e7abdf308715a5a0
2970d4696d72ec70ee67b9ef1a98e9bece9c7164685fe99968569ccd95891147
O=C([C@@H]1C[C@@H](Nc2ccccn2)CN1)N1CCCC1
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1]1-[C:2]-[C:3]-[C:4]-[C:5]-1-[C;H0;D3;+0:6](-O)=[O;D1;H0:7].[N;D1;H0:8]#[C:9]-[C:10]1-[C:11]-[C:12]-[C:13]-[NH;D2;+0:14]-1>>[N;D1;H0:8]#[C:9]-[C:10]1-[C:11]-[C:12]-[C:13]-[N;H0;D3;+0:14]-1-[C;H0;D3;+0:6](=[O;D1;H0:7])-[C:5]1-[C:4]-[C:3]-[C:2]-[NH;D2;+0:1]-1
null
[]
null
null
null
null
(2S,4R)-1-tert-Butoxycarbonyl-4-(5-cyano-2-pyridyl)aminopyrrolidine-2-carboxylic acid (title compound of Reference Example 4, 0.73 g) and (S)-2-cyanopyrrolidine hydrochloride (0.29 g) were dissolved in DMF (10 mL), and triethylamine (0.62 mL), HOBT (0.34 g) and EDC hydrochloride (0.42 g) were successively added thereto...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Carboxylic acid.Ether.Secondary amine.Boc
Tertiary amide.Secondary amine
C1CC[NH]C1.C1CCNC1
C1CCNC1.C1CC[NH]C1
c1ccncc1.C1CCNC1.C1CC[NH]C1
HO-
CN(C)C=O
null
null
CC(C)(C)OC(=O)N1C[C@H](Nc2ccc(C#N)cn2)C[C@H]1C(=O)O.N#C[C@@H]1CCCN1>CN(C)C=O>Cl.N#Cc1ccc(N[C@H]2CN[C@H](C(=O)N3CCC[C@H]3C#N)C2)nc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-d1ab302cd5a3460dbc413e2d38f638e1
CC(C)(C)OC(=O)N1C[C@@H](Nc2nc3ccccc3o2)C[C@H]1C(=O)O.N#C[C@@H]1CCCN1>>N#C[C@@H]1CCCN1C(=O)[C@@H]1C[C@H](Nc2nc3ccccc3o2)CN1
O1C(=NC2=C1C=CC=C2)N[C@H]2C[C@H](N(C2)C(=O)OC(C)(C)C)C(=O)O.Cl.C(#N)[C@H]1NCCC1>>Cl.O1C(=NC2=C1C=CC=C2)N[C@H]2C[C@H](NC2)C(=O)N2[C@@H](CCC2)C#N
CC(C)(C)OC(=O)[N:25]1[C@H:11]([C:9](O)=[O:10])[CH2:12][C@H:13]([NH:14][c:15]2[n:16][c:17]3[cH:18][cH:19][cH:20][cH:21][c:22]3[o:23]2)[CH2:24]1.[N:2]#[C:3][C@@H:4]1[CH2:5][CH2:6][CH2:7][NH:8]1>>[N:2]#[C:3][C@@H:4]1[CH2:5][CH2:6][CH2:7][N:8]1[C:9](=[O:10])[C@@H:11]1[CH2:12][C@H:13]([NH:14][c:15]2[n:16][c:17]3[cH:18][cH:1...
CC(C)(C)OC(=O)N1C[C@@H](Nc2nc3ccccc3o2)C[C@H]1C(=O)O.N#C[C@@H]1CCCN1
N#C[C@@H]1CCCN1C(=O)[C@@H]1C[C@H](Nc2nc3ccccc3o2)CN1
null
null
CN(C)C=O
Acylation
OtherReaction
0f0e880dc075a48f825a869e028ef98e81f3b02c1beed442e7abdf308715a5a0
2970d4696d72ec70ee67b9ef1a98e9bece9c7164685fe99968569ccd95891147
O=C([C@@H]1C[C@H](Nc2nc3ccccc3o2)CN1)N1CCCC1
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1]1-[C:2]-[C:3]-[C:4]-[C:5]-1-[C;H0;D3;+0:6](-O)=[O;D1;H0:7].[N;D1;H0:8]#[C:9]-[C:10]1-[C:11]-[C:12]-[C:13]-[NH;D2;+0:14]-1>>[N;D1;H0:8]#[C:9]-[C:10]1-[C:11]-[C:12]-[C:13]-[N;H0;D3;+0:14]-1-[C;H0;D3;+0:6](=[O;D1;H0:7])-[C:5]1-[C:4]-[C:3]-[C:2]-[NH;D2;+0:1]-1
null
[]
null
null
null
null
(2S,4S)-4-(2-Benzoxazolyl)amino-1-tert-butoxycarbonylpyrrolidine-2-carboxylic acid (title compound of Reference Example 5, 1.04 g) and (S)-2-cyanopyrrolidine hydrochloride (0.40 g) were dissolved in DMF (5 mL), and triethylamine (0.84 mL), HOBT (0.51 g) and EDC hydrochloride (0.63 g) were successively added thereto. Th...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Carboxylic acid.Ether.Secondary amine.Boc
Tertiary amide.Secondary amine
C1CC[NH]C1.C1CCNC1
C1CC[NH]C1.C1CCNC1
C1CC[NH]C1.C1CCNC1.c1ccc2ocnc2c1
HO-
CN(C)C=O
null
null
CC(C)(C)OC(=O)N1C[C@@H](Nc2nc3ccccc3o2)C[C@H]1C(=O)O.N#C[C@@H]1CCCN1>CN(C)C=O>N#C[C@@H]1CCCN1C(=O)[C@@H]1C[C@H](Nc2nc3ccccc3o2)CN1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-d03f60aa277241cba44e5f871f303d38
CC(C)(C)OC(=O)N1C[C@H](Nc2nc3ccccc3o2)C[C@H]1C(=O)O.N#C[C@@H]1CCCN1>>N#C[C@@H]1CCCN1C(=O)[C@@H]1C[C@@H](Nc2nc3ccccc3o2)CN1
O1C(=NC2=C1C=CC=C2)N[C@@H]2C[C@H](N(C2)C(=O)OC(C)(C)C)C(=O)O.Cl.C(#N)[C@H]1NCCC1>>Cl.O1C(=NC2=C1C=CC=C2)N[C@@H]2C[C@H](NC2)C(=O)N2[C@@H](CCC2)C#N
CC(C)(C)OC(=O)[N:25]1[C@H:11]([C:9](O)=[O:10])[CH2:12][C@@H:13]([NH:14][c:15]2[n:16][c:17]3[cH:18][cH:19][cH:20][cH:21][c:22]3[o:23]2)[CH2:24]1.[N:2]#[C:3][C@@H:4]1[CH2:5][CH2:6][CH2:7][NH:8]1>>[N:2]#[C:3][C@@H:4]1[CH2:5][CH2:6][CH2:7][N:8]1[C:9](=[O:10])[C@@H:11]1[CH2:12][C@@H:13]([NH:14][c:15]2[n:16][c:17]3[cH:18][cH...
CC(C)(C)OC(=O)N1C[C@H](Nc2nc3ccccc3o2)C[C@H]1C(=O)O.N#C[C@@H]1CCCN1
N#C[C@@H]1CCCN1C(=O)[C@@H]1C[C@@H](Nc2nc3ccccc3o2)CN1
null
null
CN(C)C=O
Acylation
OtherReaction
0f0e880dc075a48f825a869e028ef98e81f3b02c1beed442e7abdf308715a5a0
2970d4696d72ec70ee67b9ef1a98e9bece9c7164685fe99968569ccd95891147
O=C([C@@H]1C[C@@H](Nc2nc3ccccc3o2)CN1)N1CCCC1
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1]1-[C:2]-[C:3]-[C:4]-[C:5]-1-[C;H0;D3;+0:6](-O)=[O;D1;H0:7].[N;D1;H0:8]#[C:9]-[C:10]1-[C:11]-[C:12]-[C:13]-[NH;D2;+0:14]-1>>[N;D1;H0:8]#[C:9]-[C:10]1-[C:11]-[C:12]-[C:13]-[N;H0;D3;+0:14]-1-[C;H0;D3;+0:6](=[O;D1;H0:7])-[C:5]1-[C:4]-[C:3]-[C:2]-[NH;D2;+0:1]-1
null
[]
null
null
null
null
(2S,4R)-4-(2-Benzoxazolyl)amino-1-tert-butoxycarbonylpyrrolidine-2-carboxylic acid (title compound of Reference Example 6, 1.0 g) and (S)-2-cyanopyrrolidine hydrochloride (0.38 g) were dissolved in DMF (10 mL), and triethylamine (0.81 mL), HOBT (0.49 g) and EDC hydrochloride (0.61 g) were successively added thereto. Th...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Carboxylic acid.Ether.Secondary amine.Boc
Tertiary amide.Secondary amine
C1CC[NH]C1.C1CCNC1
C1CC[NH]C1.C1CCNC1
C1CC[NH]C1.C1CCNC1.c1ccc2ocnc2c1
HO-
CN(C)C=O
null
null
CC(C)(C)OC(=O)N1C[C@H](Nc2nc3ccccc3o2)C[C@H]1C(=O)O.N#C[C@@H]1CCCN1>CN(C)C=O>N#C[C@@H]1CCCN1C(=O)[C@@H]1C[C@@H](Nc2nc3ccccc3o2)CN1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-6395491b54a6412db2d538169cebcf09
C=O.CC(C)(C)OC(=O)N1C[C@@H](NCc2ccc(C#N)cc2)C[C@H]1C(=O)N1CCC[C@H]1C#N>>CN(Cc1ccc(C#N)cc1)[C@H]1C[C@@H](C(=O)N2CCC[C@H]2C#N)N(C(=O)OC(C)(C)C)C1
C(C)(C)(C)OC(=O)N1[C@@H](C[C@@H](C1)NCC1=CC=C(C=C1)C#N)C(=O)N1[C@@H](CCC1)C#N.Cl.Cl.C(#N)[C@H]1N(CCC1)C(=O)[C@H]1NC[C@H](C1)NCC1=CC=C(C=C1)C#N.C=O.C(#N)[BH3-].[Na+]>>C(C)(C)(C)OC(=O)N1[C@@H](C[C@@H](C1)N(C)CC1=CC=C(C=C1)C#N)C(=O)N1[C@@H](CCC1)C#N
O=[CH2:1].[NH:2]([CH2:3][c:4]1[cH:5][cH:6][c:7]([C:8]#[N:9])[cH:10][cH:11]1)[C@H:12]1[CH2:13][C@@H:14]([C:15](=[O:16])[N:17]2[CH2:18][CH2:19][CH2:20][C@H:21]2[C:22]#[N:23])[N:24]([C:25](=[O:26])[O:27][C:28]([CH3:29])([CH3:30])[CH3:31])[CH2:32]1>>[CH3:1][N:2]([CH2:3][c:4]1[cH:5][cH:6][c:7]([C:8]#[N:9])[cH:10][cH:11]1)[C...
C=O.CC(C)(C)OC(=O)N1C[C@@H](NCc2ccc(C#N)cc2)C[C@H]1C(=O)N1CCC[C@H]1C#N
CN(Cc1ccc(C#N)cc1)[C@H]1C[C@@H](C(=O)N2CCC[C@H]2C#N)N(C(=O)OC(C)(C)C)C1
null
null
C(C)#N.C(C)(=O)O
Heteroatom Alkylation and Arylation
Eschweiler-Clarke Secondary Amine Methylation
deb0f39510ff32c3bd75ceaf7ece4070b1f686ff120d798ccd640765025dab3c
e1fdef8fde1c506d7c9deb8fd5e6f322eceea2abce3167abcf412a1fa4fd5443
O=C([C@@H]1C[C@H](NCc2ccccc2)CN1)N1CCCC1
O=[CH2;D1;+0:1].[#7:2]-[C:3]-[C:4](-[NH;D2;+0:5]-[C:6]-[c:7])-[C:8]>>[#7:2]-[C:3]-[C:4](-[N;H0;D3;+0:5](-[CH3;D1;+0:1])-[C:6]-[c:7])-[C:8]
null
[]
null
null
1
HOUR
(S)-1-[(2S,4S)-1-tert-Butoxycarbonyl-4-(4-cyanophenylmethyl)amino-2-pyrrolidinylcarbonyl]-2-cyanopyrrolidine [product of Example 31 (1), 1.04 g] and 37% formaldehyde solution (0.7 mL) were dissolved in acetonitrile (15 mL), and the mixture was stirred at room temperature for 1 hr. Sodium cyanoborohydride (0.240 g) and ...
10.6084/m9.figshare.5104873.v1
null
Formaldehyde.Secondary amine
Tertiary amine
null
null
c1ccccc1.C1CC[NH]C1.C1CC[NH]C1
Other
C(C)#N.C(C)(=O)O
null
1
C=O.CC(C)(C)OC(=O)N1C[C@@H](NCc2ccc(C#N)cc2)C[C@H]1C(=O)N1CCC[C@H]1C#N>C(C)#N.C(C)(=O)O>CN(Cc1ccc(C#N)cc1)[C@H]1C[C@@H](C(=O)N2CCC[C@H]2C#N)N(C(=O)OC(C)(C)C)C1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-4847b7bcabea4e71a27ae3755e210c13
CC(C)(C)OC(=O)N1C[C@@H](NC(=O)c2ccccc2)C[C@H]1C(=O)O.N#C[C@@H]1CCCN1>>N#C[C@@H]1CCCN1C(=O)[C@@H]1C[C@H](NC(=O)c2ccccc2)CN1
C(C1=CC=CC=C1)(=O)N[C@H]1C[C@H](N(C1)C(=O)OC(C)(C)C)C(=O)O.Cl.C(#N)[C@H]1NCCC1>>Cl.C(C1=CC=CC=C1)(=O)N[C@H]1C[C@H](NC1)C(=O)N1[C@@H](CCC1)C#N
CC(C)(C)OC(=O)[N:24]1[C@H:11]([C:9](O)=[O:10])[CH2:12][C@H:13]([NH:14][C:15](=[O:16])[c:17]2[cH:18][cH:19][cH:20][cH:21][cH:22]2)[CH2:23]1.[N:2]#[C:3][C@@H:4]1[CH2:5][CH2:6][CH2:7][NH:8]1>>[N:2]#[C:3][C@@H:4]1[CH2:5][CH2:6][CH2:7][N:8]1[C:9](=[O:10])[C@@H:11]1[CH2:12][C@H:13]([NH:14][C:15](=[O:16])[c:17]2[cH:18][cH:19]...
CC(C)(C)OC(=O)N1C[C@@H](NC(=O)c2ccccc2)C[C@H]1C(=O)O.N#C[C@@H]1CCCN1
N#C[C@@H]1CCCN1C(=O)[C@@H]1C[C@H](NC(=O)c2ccccc2)CN1
null
null
CN(C)C=O
Acylation
OtherReaction
0f0e880dc075a48f825a869e028ef98e81f3b02c1beed442e7abdf308715a5a0
2970d4696d72ec70ee67b9ef1a98e9bece9c7164685fe99968569ccd95891147
O=C(N[C@@H]1CN[C@H](C(=O)N2CCCC2)C1)c1ccccc1
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1]1-[C:2]-[C:3]-[C:4]-[C:5]-1-[C;H0;D3;+0:6](-O)=[O;D1;H0:7].[N;D1;H0:8]#[C:9]-[C:10]1-[C:11]-[C:12]-[C:13]-[NH;D2;+0:14]-1>>[N;D1;H0:8]#[C:9]-[C:10]1-[C:11]-[C:12]-[C:13]-[N;H0;D3;+0:14]-1-[C;H0;D3;+0:6](=[O;D1;H0:7])-[C:5]1-[C:4]-[C:3]-[C:2]-[NH;D2;+0:1]-1
null
[]
null
null
null
null
(2S,4S)-4-Benzoylamino-1-tert-butoxycarbonylpyrrolidine-2-carboxylic acid (title compound of Reference Example 7, 1.1 g) and (S)-2-cyanopyrrolidine hydrochloride (0.44 g) were dissolved in DMF (10 mL), and triethylamine (0.98 mL), HOBT (0.54 g) and EDC hydrochloride (0.67 g) were successively added. The mixture was sti...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Carboxylic acid.Ether.Secondary amine.Boc
Tertiary amide.Secondary amine
C1CC[NH]C1.C1CCNC1
C1CC[NH]C1.C1CCNC1
C1CC[NH]C1.C1CCNC1.c1ccccc1
HO-
CN(C)C=O
null
null
CC(C)(C)OC(=O)N1C[C@@H](NC(=O)c2ccccc2)C[C@H]1C(=O)O.N#C[C@@H]1CCCN1>CN(C)C=O>N#C[C@@H]1CCCN1C(=O)[C@@H]1C[C@H](NC(=O)c2ccccc2)CN1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-defa255eef994bfa94bf4e3fc64a8ca9
CC(C)(C)OC(=O)N1C[C@H](NC(=O)c2ccccc2)C[C@H]1C(=O)O.N#C[C@@H]1CCCN1>>N#C[C@@H]1CCCN1C(=O)[C@@H]1C[C@@H](NC(=O)c2ccccc2)CN1
C(C1=CC=CC=C1)(=O)N[C@@H]1C[C@H](N(C1)C(=O)OC(C)(C)C)C(=O)O.Cl.C(#N)[C@H]1NCCC1>>Cl.C(C1=CC=CC=C1)(=O)N[C@@H]1C[C@H](NC1)C(=O)N1[C@@H](CCC1)C#N
CC(C)(C)OC(=O)[N:24]1[C@H:11]([C:9](O)=[O:10])[CH2:12][C@@H:13]([NH:14][C:15](=[O:16])[c:17]2[cH:18][cH:19][cH:20][cH:21][cH:22]2)[CH2:23]1.[N:2]#[C:3][C@@H:4]1[CH2:5][CH2:6][CH2:7][NH:8]1>>[N:2]#[C:3][C@@H:4]1[CH2:5][CH2:6][CH2:7][N:8]1[C:9](=[O:10])[C@@H:11]1[CH2:12][C@@H:13]([NH:14][C:15](=[O:16])[c:17]2[cH:18][cH:1...
CC(C)(C)OC(=O)N1C[C@H](NC(=O)c2ccccc2)C[C@H]1C(=O)O.N#C[C@@H]1CCCN1
N#C[C@@H]1CCCN1C(=O)[C@@H]1C[C@@H](NC(=O)c2ccccc2)CN1
null
null
CN(C)C=O
Acylation
OtherReaction
0f0e880dc075a48f825a869e028ef98e81f3b02c1beed442e7abdf308715a5a0
2970d4696d72ec70ee67b9ef1a98e9bece9c7164685fe99968569ccd95891147
O=C(N[C@H]1CN[C@H](C(=O)N2CCCC2)C1)c1ccccc1
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1]1-[C:2]-[C:3]-[C:4]-[C:5]-1-[C;H0;D3;+0:6](-O)=[O;D1;H0:7].[N;D1;H0:8]#[C:9]-[C:10]1-[C:11]-[C:12]-[C:13]-[NH;D2;+0:14]-1>>[N;D1;H0:8]#[C:9]-[C:10]1-[C:11]-[C:12]-[C:13]-[N;H0;D3;+0:14]-1-[C;H0;D3;+0:6](=[O;D1;H0:7])-[C:5]1-[C:4]-[C:3]-[C:2]-[NH;D2;+0:1]-1
null
[]
null
null
null
null
(2S,4R)-4-Benzoylamino-1-tert-butoxycarbonylpyrrolidine-2-carboxylic acid (title compound of Reference Example 8, 1.6 g) and (S)-2-cyanopyrrolidine hydrochloride (0.63 g) were dissolved in DMF (10 mL), and triethylamine (1.32 mL), HOBT (0.79 g) and EDC hydrochloride (0.99 g) were successively added. The mixture was sti...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Carboxylic acid.Ether.Secondary amine.Boc
Tertiary amide.Secondary amine
C1CC[NH]C1.C1CCNC1
C1CC[NH]C1.C1CCNC1
C1CC[NH]C1.C1CCNC1.c1ccccc1
HO-
CN(C)C=O
null
null
CC(C)(C)OC(=O)N1C[C@H](NC(=O)c2ccccc2)C[C@H]1C(=O)O.N#C[C@@H]1CCCN1>CN(C)C=O>N#C[C@@H]1CCCN1C(=O)[C@@H]1C[C@@H](NC(=O)c2ccccc2)CN1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-d1a44d6bc3cc472b913ff26449bf5948
C=O.CC(C)(C)OC(=O)N1C[C@@H](NCc2ccc(C#N)cc2)C[C@H]1C(=O)N1CCSC1>>CN(Cc1ccc(C#N)cc1)[C@H]1C[C@@H](C(=O)N2CCSC2)N(C(=O)OC(C)(C)C)C1
C(C)(C)(C)OC(=O)N1[C@@H](C[C@@H](C1)NCC1=CC=C(C=C1)C#N)C(=O)N1CSCC1.Cl.Cl.C(#N)C1=CC=C(C=C1)CN[C@H]1C[C@H](NC1)C(=O)N1CSCC1.C=O.C(#N)[BH3-].[Na+]>>C(C)(C)(C)OC(=O)N1[C@@H](C[C@@H](C1)N(C)CC1=CC=C(C=C1)C#N)C(=O)N1CSCC1
O=[CH2:1].[NH:2]([CH2:3][c:4]1[cH:5][cH:6][c:7]([C:8]#[N:9])[cH:10][cH:11]1)[C@H:12]1[CH2:13][C@@H:14]([C:15](=[O:16])[N:17]2[CH2:18][CH2:19][S:20][CH2:21]2)[N:22]([C:23](=[O:24])[O:25][C:26]([CH3:27])([CH3:28])[CH3:29])[CH2:30]1>>[CH3:1][N:2]([CH2:3][c:4]1[cH:5][cH:6][c:7]([C:8]#[N:9])[cH:10][cH:11]1)[C@H:12]1[CH2:13]...
C=O.CC(C)(C)OC(=O)N1C[C@@H](NCc2ccc(C#N)cc2)C[C@H]1C(=O)N1CCSC1
CN(Cc1ccc(C#N)cc1)[C@H]1C[C@@H](C(=O)N2CCSC2)N(C(=O)OC(C)(C)C)C1
null
C(C)(=O)O
C(C)#N
Heteroatom Alkylation and Arylation
Eschweiler-Clarke Secondary Amine Methylation
deb0f39510ff32c3bd75ceaf7ece4070b1f686ff120d798ccd640765025dab3c
e1fdef8fde1c506d7c9deb8fd5e6f322eceea2abce3167abcf412a1fa4fd5443
O=C([C@@H]1C[C@H](NCc2ccccc2)CN1)N1CCSC1
O=[CH2;D1;+0:1].[#7:2]-[C:3]-[C:4](-[NH;D2;+0:5]-[C:6]-[c:7])-[C:8]>>[#7:2]-[C:3]-[C:4](-[N;H0;D3;+0:5](-[CH3;D1;+0:1])-[C:6]-[c:7])-[C:8]
null
[]
null
null
30
MINUTE
3-[(2S,4S)-1-tert-Butoxycarbonyl-4-(4-cyanophenylmethyl)amino-2-pyrrolidinylcarbonyl]-1,3-thiazolidine [product of Example 63 (1), 1.35 g] and 37% formaldehyde solution (0.788 mL) were dissolved in acetonitrile (20 mL), and the mixture was stirred at room temperature for 30 min. Sodium cyanoborohydride (0.305 g) and se...
10.6084/m9.figshare.5104873.v1
null
Formaldehyde.Secondary amine
Tertiary amine
null
null
c1ccccc1.C1CC[NH]C1.C1CSC[NH]1
Other
C(C)(=O)O.C(C)#N
null
0.5
C=O.CC(C)(C)OC(=O)N1C[C@@H](NCc2ccc(C#N)cc2)C[C@H]1C(=O)N1CCSC1>C(C)(=O)O.C(C)#N>CN(Cc1ccc(C#N)cc1)[C@H]1C[C@@H](C(=O)N2CCSC2)N(C(=O)OC(C)(C)C)C1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-a12d8afff4e34429af22e1d224db33ae
O=C([C@@H]1C[C@H](Nc2ccc([N+](=O)[O-])cc2)CN1)N1CCSC1>>Nc1ccc(N[C@@H]2CN[C@H](C(=O)N3CCSC3)C2)cc1
Cl.[N+](=O)([O-])C1=CC=C(C=C1)N[C@H]1C[C@H](NC1)C(=O)N1CSCC1.Cl.O1CCOCC1>>Cl.NC1=CC=C(C=C1)N[C@H]1C[C@H](NC1)C(=O)N1CSCC1
O=[N+:2]([O-])[c:3]1[cH:4][cH:5][c:6]([NH:7][C@@H:8]2[CH2:9][NH:10][C@H:11]([C:12](=[O:13])[N:14]3[CH2:15][CH2:16][S:17][CH2:18]3)[CH2:19]2)[cH:20][cH:21]1>>[NH2:2][c:3]1[cH:4][cH:5][c:6]([NH:7][C@@H:8]2[CH2:9][NH:10][C@H:11]([C:12](=[O:13])[N:14]3[CH2:15][CH2:16][S:17][CH2:18]3)[CH2:19]2)[cH:20][cH:21]1
O=C([C@@H]1C[C@H](Nc2ccc([N+](=O)[O-])cc2)CN1)N1CCSC1
Nc1ccc(N[C@@H]2CN[C@H](C(=O)N3CCSC3)C2)cc1
null
[Pd]
C(C)O
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
O=C([C@@H]1C[C@H](Nc2ccccc2)CN1)N1CCSC1
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
7.1
[{"value": 7.1, "product": "Cl.NC1=CC=C(C=C1)N[C@H]1C[C@H](NC1)C(=O)N1CSCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
18
HOUR
The title compound (200 mg) of Example 55 was dissolved in ethanol (10 mL), and 4 mol/L hydrochloric acid-1,4-dioxane (0.28 mL) and 10% palladium/carbon (100 mg) were added. The mixture was stirred under a hydrogen atomosphere (1 atm) at room temperature for 18 hr. The reaction mixture was filtrated and the filtrate wa...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1ccccc1.C1CCNC1.C1CSC[NH]1
Other
[Pd].C(C)O
null
18
O=C([C@@H]1C[C@H](Nc2ccc([N+](=O)[O-])cc2)CN1)N1CCSC1>[Pd].C(C)O>Nc1ccc(N[C@@H]2CN[C@H](C(=O)N3CCSC3)C2)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-d420f37c18ae4fd8aae271345f20a892
FC(F)(F)c1ccc(Cl)nc1>>[O-][n+]1cc(C(F)(F)F)ccc1Cl
ClC1=CC(=CC=C1)C(=O)OO.ClC1=NC=C(C=C1)C(F)(F)F.S(=S)(=O)([O-])[O-].[Na+].[Na+].C(O)([O-])=O.[Na+]>>ClC1=[N+](C=C(C=C1)C(F)(F)F)[O-]
[n:2]1[cH:3][c:4]([C:5]([F:6])([F:7])[F:8])[cH:9][cH:10][c:11]1[Cl:12]>>[O-:1][n+:2]1[cH:3][c:4]([C:5]([F:6])([F:7])[F:8])[cH:9][cH:10][c:11]1[Cl:12]
FC(F)(F)c1ccc(Cl)nc1
[O-][n+]1cc(C(F)(F)F)ccc1Cl
null
null
C(Cl)(Cl)Cl
Functional Group Interconversion
OtherReaction
54415aed4bb61f76efee9ed140374352608210a9fed7c372975c12eb7023cea2
f1bbf9aa3c82f5e49be9f6d53533b6bb152f359232b6d32090c168949766aa71
c1cc[nH+]cc1
[Cl;D1;H0:1]-[c:2](:[c:3]):[n;H0;D2;+0:4]:[c:5]:[c:6]>>[Cl;D1;H0:1]-[c:2](:[c:3]):[n+;H0;D3:4](-[O;-;D1;H0:7]):[c:5]:[c:6]
11.8
[{"value": 11.8, "product": "ClC1=[N+](C=C(C=C1)C(F)(F)F)[O-]", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
60
CELSIUS
30
HOUR
2-Chloro-5-trifluoromethylpyridine (5 g) was dissolved in chloroform (150 mL) and m-chloroperbenzoic acid (14.3 g) was added thereto. The mixture was stirred at 60° C. for 30 hr. Aqueous sodium thiosulfate solution and saturated aqueous sodium hydrogencarbonate solution were added to the reaction mixture, and after sti...
10.6084/m9.figshare.5104873.v1
null
null
null
c1ccncc1
C1=CC=[NH+]C=C1
C1=CC=[NH+]C=C1
null
C(Cl)(Cl)Cl
60
30
FC(F)(F)c1ccc(Cl)nc1>C(Cl)(Cl)Cl>[O-][n+]1cc(C(F)(F)F)ccc1Cl
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-999a2d1f33744c50bceba70860d4b33a
N#Cc1ccc(Cl)nc1.OO>>N#Cc1ccc(Cl)[n+]([O-])c1
FC(C(=O)OC(C(F)(F)F)=O)(F)F.OO.NC(=O)N.ClC1=NC=C(C=C1)C#N.S(=S)(=O)([O-])[O-].[Na+].[Na+]>>ClC1=[N+](C=C(C=C1)C#N)[O-]
[N:1]#[C:2][c:3]1[cH:4][cH:5][c:6]([Cl:7])[n:8][cH:10]1.O[OH:9]>>[N:1]#[C:2][c:3]1[cH:4][cH:5][c:6]([Cl:7])[n+:8]([O-:9])[cH:10]1
N#Cc1ccc(Cl)nc1.OO
N#Cc1ccc(Cl)[n+]([O-])c1
null
null
C(C)#N
Functional Group Interconversion
OtherReaction
d7f3c84fb751fef5567bc0e84a2e7c0afb271257e8dfb17aa871e038ff1a84c7
bf536f3bf8ed7b8faf08cf1c004ccd0a5e7fe59339402dd73ac837bb4a52f2ba
c1cc[nH+]cc1
O-[OH;D1;+0:1].[Cl;D1;H0:2]-[c:3](:[c:4]):[n;H0;D2;+0:5]:[c:6]:[c:7]>>[Cl;D1;H0:2]-[c:3](:[c:4]):[n+;H0;D3:5](-[O-;H0;D1:1]):[c:6]:[c:7]
null
[]
null
null
18
HOUR
2-Chloropyridine-5-carbonitrile (7.01 g) was dissolved in acetonitrile (70 mL), and urea hydrogen peroxide addition compound (10 g) was added. Trifluoroacetic anhydride was added dropwise to the reaction mixture under ice-cooling and the mixture was stirred at room temperature for 18 hr. The reaction mixture was added ...
10.6084/m9.figshare.5104873.v1
null
Peroxide
null
c1ccncc1
C1=CC=[NH+]C=C1
C1=CC=[NH+]C=C1
HO-
C(C)#N
null
18
N#Cc1ccc(Cl)nc1.OO>C(C)#N>N#Cc1ccc(Cl)[n+]([O-])c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-a7776923fa85494fafd076a7edc9fc9f
BrCc1ccccc1.CC(C)(C)OC(=O)N1C[C@@H](Nc2ccc(C#N)cn2)C[C@H]1C(=O)N1CCSC1>>CC(C)(C)OC(=O)N1C[C@@H](N(Cc2ccccc2)c2ccc(C#N)cn2)C[C@H]1C(=O)N1CCSC1
C(C1=CC=CC=C1)Br.C(C)(C)(C)OC(=O)N1[C@@H](C[C@@H](C1)NC1=NC=C(C=C1)C#N)C(=O)N1CSCC1.C(CC(O)(C(=O)O)CC(=O)O)(=O)O.CC(C)([O-])C.[K+]>>C(C1=CC=CC=C1)N(C1=NC=C(C=C1)C#N)[C@H]1C[C@H](N(C1)C(=O)OC(C)(C)C)C(=O)N1CSCC1
Br[CH2:12][c:13]1[cH:14][cH:15][cH:16][cH:17][cH:18]1.[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][C@@H:10]([NH:11][c:19]2[cH:20][cH:21][c:22]([C:23]#[N:24])[cH:25][n:26]2)[CH2:27][C@H:28]1[C:29](=[O:30])[N:31]1[CH2:32][CH2:33][S:34][CH2:35]1>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:...
BrCc1ccccc1.CC(C)(C)OC(=O)N1C[C@@H](Nc2ccc(C#N)cn2)C[C@H]1C(=O)N1CCSC1
CC(C)(C)OC(=O)N1C[C@@H](N(Cc2ccccc2)c2ccc(C#N)cn2)C[C@H]1C(=O)N1CCSC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
6d58cac08ccced0a33ed16fbca180bc12aa011288d6476106d98a7b2cbc3d709
523d37155b42c8dc851abeddadebb241cdd90bdf649ba750c35e13c8c752d7b0
O=C([C@@H]1C[C@H](N(Cc2ccccc2)c2ccccn2)CN1)N1CCSC1
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[#7:5]-[C:6]-[C:7](-[NH;D2;+0:8]-[c:9](:[c:10]):[#7;a:11]:[c:12])-[C:13]>>[#7:5]-[C:6]-[C:7](-[N;H0;D3;+0:8](-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4])-[c:9](:[c:10]):[#7;a:11]:[c:12])-[C:13]
null
[]
null
null
10
MINUTE
3-[(2S,4S)-1-tert-Butoxycarbonyl-4-(5-cyano-2-pyridyl)amino-2-pyrrolidinylcarbonyl]-1,3-thiazolidine [product of Example 58(1)] (305 mg) was dissolved in DMF (10 mL), and potassium tert-butoxide (93 mg) was added under ice cooling. After stirring the mixture for 10 min, benzyl bromide (94 μl) was added, and the mixture...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amine
Tertiary amine
null
null
C1CC[NH]C1.c1ccccc1.c1ccncc1.C1CSC[NH]1
HBr
CN(C)C=O
null
0.166667
BrCc1ccccc1.CC(C)(C)OC(=O)N1C[C@@H](Nc2ccc(C#N)cn2)C[C@H]1C(=O)N1CCSC1>CN(C)C=O>CC(C)(C)OC(=O)N1C[C@@H](N(Cc2ccccc2)c2ccc(C#N)cn2)C[C@H]1C(=O)N1CCSC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-cf76bdab7fe6409e9a5ea4cc18b9883f
CCN(C(C)C)C(C)C.N#Cc1ccc(CN[C@@H]2CN[C@H](C(=O)N3CCSC3)C2)cc1.OCCBr>>CC(C)(C)OC(=O)N1C[C@@H](N(CCO)Cc2ccc(C#N)cc2)C[C@H]1C(=O)N1CCSC1
C(O)([O-])=O.[Na+].BrCCO.C(C)(C)N(CC)C(C)C.Cl.Cl.C(#N)C1=CC=C(C=C1)CN[C@H]1C[C@H](NC1)C(=O)N1CSCC1.CN1C(CCC1)=O>>C(C)(C)(C)OC(=O)N1[C@@H](C[C@@H](C1)N(CCO)CC1=CC=C(C=C1)C#N)C(=O)N1CSCC1
CCN(C(C)[CH3:4])[CH:2]([CH3:1])[CH3:3].[NH:8]1[CH2:9][C@@H:10]([NH:11][CH2:15][c:16]2[cH:17][cH:18][c:19]([C:20]#[N:21])[cH:22][cH:23]2)[CH2:24][C@H:25]1[C:26](=[O:27])[N:28]1[CH2:29][CH2:30][S:31][CH2:32]1.Br[CH2:12][CH2:13][OH:14]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][C@@H:10]([N:11]([CH2:12]...
CCN(C(C)C)C(C)C.N#Cc1ccc(CN[C@@H]2CN[C@H](C(=O)N3CCSC3)C2)cc1.OCCBr
CC(C)(C)OC(=O)N1C[C@@H](N(CCO)Cc2ccc(C#N)cc2)C[C@H]1C(=O)N1CCSC1
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
d8a307254dc3bc6e195371883ab2dcb9c63e02e01e71116906b5082e7b8a3200
23d66b49c456aba6d2ef193a6aa42c9f8b3e98a106c32c8e4e3d9ccc98c1a74b
O=C([C@@H]1C[C@H](NCc2ccccc2)CN1)N1CCSC1
Br-[CH2;D2;+0:1]-[C:2]-[O;D1;H1:3].C-C-N(-C(-C)-[CH3;D1;+0:4])-[CH;D3;+0:5](-[C;D1;H3:6])-[C;D1;H3:7].[#16:8]-[C:9]-[#7:10](-[C:11](=[O;D1;H0:12])-[C:13]1-[C:14]-[C:15](-[NH;D2;+0:16]-[C:17]-[c:18])-[C:19]-[NH;D2;+0:20]-1)-[C:21]>>[#16:8]-[C:9]-[#7:10](-[C:11](=[O;D1;H0:12])-[C:13]1-[C:14]-[C:15](-[N;H0;D3;+0:16](-[C:1...
null
[]
80
CELSIUS
2
DAY
The product (1.67 g) of Example 63 (1) was dissolved in N-methyl-2-pyrrolidone (12 mL), and 2-bromoethanol (1.42 mL) and diisopropylethylamine (2.09 mL) were added thereto. The mixture was stirred at 80° C. for 2 days. The reaction mixture was added to saturated aqueous sodium hydrogencarbonate solution and the mixture...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amine.Secondary amine.Tertiary amine
Carbamic ester.Ether.Tertiary amine.Boc
C1CCNC1
C1CC[NH]C1
C1CC[NH]C1.c1ccccc1.C1CSC[NH]1
HBr
null
80
48
CCN(C(C)C)C(C)C.N#Cc1ccc(CN[C@@H]2CN[C@H](C(=O)N3CCSC3)C2)cc1.OCCBr>>CC(C)(C)OC(=O)N1C[C@@H](N(CCO)Cc2ccc(C#N)cc2)C[C@H]1C(=O)N1CCSC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-4a2f1cb2330a4ca7b53b094e463eda13
CCN(C(C)C)C(C)C.CCOC(=O)CBr.CN1CCCC1=O.N#Cc1ccc(CN[C@@H]2CN[C@H](C(=O)N3CCSC3)C2)cc1.O=C([O-])O>>CCOC(=O)CN(Cc1ccc(C#N)cc1)[C@H]1C[C@@H](C(=O)N2CCSC2)N(C(=O)OC(C)(C)C)C1
C(O)([O-])=O.[Na+].BrCC(=O)OCC.C(C)(C)N(CC)C(C)C.Cl.Cl.C(#N)C1=CC=C(C=C1)CN[C@H]1C[C@H](NC1)C(=O)N1CSCC1.CN1C(CCC1)=O>>C(C)(C)(C)OC(=O)N1[C@@H](C[C@@H](C1)N(CC(=O)OCC)CC1=CC=C(C=C1)C#N)C(=O)N1CSCC1
CC(C)N(C[CH3:32])C([CH3:33])[CH3:34].Br[CH2:6][C:4]([O:3][CH2:2][CH3:1])=[O:5].O=C1CCCN1[CH3:31].[NH:7]([CH2:8][c:9]1[cH:10][cH:11][c:12]([C:13]#[N:14])[cH:15][cH:16]1)[C@H:17]1[CH2:18][C@@H:19]([C:20](=[O:21])[N:22]2[CH2:23][CH2:24][S:25][CH2:26]2)[NH:27][CH2:35]1.[O-][C:28](=[O:29])[OH:30]>>[CH3:1][CH2:2][O:3][C:4](=...
CCN(C(C)C)C(C)C.CCOC(=O)CBr.CN1CCCC1=O.N#Cc1ccc(CN[C@@H]2CN[C@H](C(=O)N3CCSC3)C2)cc1.O=C([O-])O
CCOC(=O)CN(Cc1ccc(C#N)cc1)[C@H]1C[C@@H](C(=O)N2CCSC2)N(C(=O)OC(C)(C)C)C1
null
null
null
C-C Coupling
OtherReaction
c34b37c1c3456c4cc5767c06a849a038b92593613830dabf5bbb3d79137a5f76
d0c137067a29add8cdf05b563209a5df4ae9b3038bbd325e8cf2afe78f23ca5a
O=C([C@@H]1C[C@H](NCc2ccccc2)CN1)N1CCSC1
Br-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C:5].C-C(-C)-N(-C-[CH3;D1;+0:6])-C(-[CH3;D1;+0:7])-[CH3;D1;+0:8].O=C1-C-C-C-N-1-[CH3;D1;+0:9].[#16:10]-[C:11]-[#7:12](-[C:13](=[O;D1;H0:14])-[C:15]1-[C:16]-[C:17](-[NH;D2;+0:18]-[C:19]-[c:20])-[C:21]-[NH;D2;+0:22]-1)-[C:23].[O-]-[C;H0;D3;+0:24](=[O;D1;H0:25])-[OH;D1;+0:26]>>...
null
[]
null
null
18
HOUR
The product (0.833 g) of Example 63 (1) was dissolved in N-methyl-2-pyrrolidone (6 mL), and ethyl bromoacetate (0.333 mL) and diisopropylethylamine (1.05 mL) were added thereto. The mixture was stirred at room temperature for 18 hr. The reaction mixture was added to saturated aqueous sodium hydrogencarbonate solution, ...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Carbonic Acid.Ester.Tertiary amide.Secondary amine.Secondary amine.Tertiary amine
Carbamic ester.Ester.Ether.Tertiary amine.Boc
C1CCNC1.C1CCNC1
C1CC[NH]C1
c1ccccc1.C1CC[NH]C1.C1CSC[NH]1
HBr
null
null
18
CCN(C(C)C)C(C)C.CCOC(=O)CBr.CN1CCCC1=O.N#Cc1ccc(CN[C@@H]2CN[C@H](C(=O)N3CCSC3)C2)cc1.O=C([O-])O>>CCOC(=O)CN(Cc1ccc(C#N)cc1)[C@H]1C[C@@H](C(=O)N2CCSC2)N(C(=O)OC(C)(C)C)C1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-d78402d1c48e463d8efe9e734f7ec81b
CC(C)(C)OC(=O)N1C[C@@H](NS(=O)(=O)c2ccc(C#N)cc2)C[C@H]1C(=O)N1CCSC1.N#Cc1ccc(CBr)cc1>>CC(C)(C)OC(=O)N1C[C@@H](N(Cc2ccc(C#N)cc2)S(=O)(=O)c2ccc(C#N)cc2)C[C@H]1C(=O)N1CCSC1
C(C)(C)(C)OC(=O)N1[C@@H](C[C@@H](C1)NS(=O)(=O)C1=CC=C(C=C1)C#N)C(=O)N1CSCC1.Cl.C(#N)C1=CC=C(C=C1)S(=O)(=O)N[C@H]1C[C@H](NC1)C(=O)N1CSCC1.C([O-])([O-])=O.[K+].[K+].C(#N)C1=CC=C(CBr)C=C1.C(CC(O)(C(=O)O)CC(=O)O)(=O)O>>C(C)(C)(C)OC(=O)N1[C@@H](C[C@@H](C1)N(S(=O)(=O)C1=CC=C(C=C1)C#N)CC1=CC=C(C=C1)C#N)C(=O)N1CSCC1
[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][C@@H:10]([NH:11][S:21](=[O:22])(=[O:23])[c:24]2[cH:25][cH:26][c:27]([C:28]#[N:29])[cH:30][cH:31]2)[CH2:32][C@H:33]1[C:34](=[O:35])[N:36]1[CH2:37][CH2:38][S:39][CH2:40]1.Br[CH2:12][c:13]1[cH:14][cH:15][c:16]([C:17]#[N:18])[cH:19][cH:20]1>>[CH3:1][C:2]([CH3:3]...
CC(C)(C)OC(=O)N1C[C@@H](NS(=O)(=O)c2ccc(C#N)cc2)C[C@H]1C(=O)N1CCSC1.N#Cc1ccc(CBr)cc1
CC(C)(C)OC(=O)N1C[C@@H](N(Cc2ccc(C#N)cc2)S(=O)(=O)c2ccc(C#N)cc2)C[C@H]1C(=O)N1CCSC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
0fe6648877a29ae177a907a0d252f35d8beab440bf428116c5424a67bc0e72cd
0b054affe7e4bb904ceae512aabc19d89c93551cb46dfbc6f220fc85e5eeff75
O=C([C@@H]1C[C@H](N(Cc2ccccc2)S(=O)(=O)c2ccccc2)CN1)N1CCSC1
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[#7:5]-[C:6]-[C:7](-[NH;D2;+0:8]-[#16:9](=[O;D1;H0:10])(=[O;D1;H0:11])-[c:12])-[C:13]>>[#7:5]-[C:6]-[C:7](-[N;H0;D3;+0:8](-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4])-[#16:9](=[O;D1;H0:10])(=[O;D1;H0:11])-[c:12])-[C:13]
84.3
[{"value": 84.3, "product": "C(C)(C)(C)OC(=O)N1[C@@H](C[C@@H](C1)N(S(=O)(=O)C1=CC=C(C=C1)C#N)CC1=CC=C(C=C1)C#N)C(=O)N1CSCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
4
HOUR
3-[(2S,4S)-1-tert-Butoxycarbonyl-4-(4-cyanophenylsulfonyl)amino-2-pyrrolidinylcarbonyl]-1,3-thiazolidine [product of Example 123 (1), 856 mg] was dissolved in DMF (20 mL), and potassium carbonate (380 mg) and 4-cyanobenzyl bromide (400 mg) were added thereto at room temperature. The mixture was stirred for 4 hr. To the...
10.6084/m9.figshare.5104873.v1
null
Sulfonamide.Primary halide
Tertiary amine
null
null
C1CC[NH]C1.c1ccccc1.c1ccccc1.C1CSC[NH]1
HBr
CN(C)C=O
null
4
CC(C)(C)OC(=O)N1C[C@@H](NS(=O)(=O)c2ccc(C#N)cc2)C[C@H]1C(=O)N1CCSC1.N#Cc1ccc(CBr)cc1>CN(C)C=O>CC(C)(C)OC(=O)N1C[C@@H](N(Cc2ccc(C#N)cc2)S(=O)(=O)c2ccc(C#N)cc2)C[C@H]1C(=O)N1CCSC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-e85e41b6af834b57955dea0a08467d75
CC(C)(C)OC(=O)N1CCC(=O)CC1.c1ccc2c(c1)CCN2>>CC(C)(C)OC(=O)N1CCC(N2CCc3ccccc32)CC1
C(C)(=O)O[BH-](OC(C)=O)OC(C)=O.[Na+].C(C)(C)(C)OC(=O)N1CCC(CC1)=O.N1CCC2=CC=CC=C12.C(C)(=O)O>>C(C)(C)(C)OC(=O)N1CCC(CC1)N1CCC2=CC=CC=C12
O=[C:11]1[CH2:10][CH2:9][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:22][CH2:21]1.[NH:12]1[CH2:13][CH2:14][c:15]2[cH:16][cH:17][cH:18][cH:19][c:20]21>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][CH2:10][CH:11]([N:12]2[CH2:13][CH2:14][c:15]3[cH:16][cH:17][cH:18][cH:19][c:20]32)[CH2:21][C...
CC(C)(C)OC(=O)N1CCC(=O)CC1.c1ccc2c(c1)CCN2
CC(C)(C)OC(=O)N1CCC(N2CCc3ccccc32)CC1
null
null
O.ClCCCl
Heteroatom Alkylation and Arylation
OtherReaction
ed5f829465aab8e8fa321fc868dfe3231b2d42ce59513bacd6302db66ad15586
99acf13bfcfe579f51ccb82c65e4ca039ee7ca9b6fcd2747a3d9a292a88e564e
c1ccc2c(c1)CCN2C1CCNCC1
O=[C;H0;D3;+0:1]1-[C:2]-[C:3]-[#7:4]-[C:5]-[C:6]-1.[c:7]:[c:8]1:[c:9]-[C:10]-[C:11]-[NH;D2;+0:12]-1>>[c:7]:[c:8]1:[c:9]-[C:10]-[C:11]-[N;H0;D3;+0:12]-1-[CH;D3;+0:1]1-[C:2]-[C:3]-[#7:4]-[C:5]-[C:6]-1
74.3
[{"value": 74.3, "product": "C(C)(C)(C)OC(=O)N1CCC(CC1)N1CCC2=CC=CC=C12", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
12
HOUR
1-tert-Butoxycarbonylpiperidin-4-one (2.50 g), indoline (1.50 g) and acetic acid (0.73 mL) were dissolved in 1,2-dichloroethane (75 mL), and sodium triacetoxyborohydride (5.32 g) was added thereto. The mixture was stirred at room temperature for 12 hr. The reaction mixture was added to iced water and the mixture was ex...
10.6084/m9.figshare.5104873.v1
null
Ketone.Secondary amine
Tertiary amine
C1CC[NH]CC1.c1ccc2c(c1)CCN2
C1CC[NH]CC1.c1ccc2c(c1)CC[NH]2
C1CC[NH]CC1.c1ccc2c(c1)CC[NH]2
Other
O.ClCCCl
null
12
CC(C)(C)OC(=O)N1CCC(=O)CC1.c1ccc2c(c1)CCN2>O.ClCCCl>CC(C)(C)OC(=O)N1CCC(N2CCc3ccccc32)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-cdc8330fdabf4b8090f409cf85b62274
CC(C)(C)OC(=O)N1CCN(N)CC1.O=[N+]([O-])c1ccc(F)cc1>>CC(C)(C)OC(=O)N1CCC(Nc2ccc([N+](=O)[O-])cc2)CC1
O.NN1CCN(CC1)C(=O)OC(C)(C)C.FC1=CC=C(C=C1)[N+](=O)[O-].C(C)(C)N(C(C)C)CC>>C(C)(C)(C)OC(=O)N1CCC(CC1)NC1=CC=C(C=C1)[N+](=O)[O-]
N1([NH2:12])[CH2:10][CH2:9][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:23][CH2:22]1.F[c:13]1[cH:14][cH:15][c:16]([N+:17](=[O:18])[O-:19])[cH:20][cH:21]1>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][CH2:10][CH:11]([NH:12][c:13]2[cH:14][cH:15][c:16]([N+:17](=[O:18])[O-:19])[cH:20][cH:21]...
CC(C)(C)OC(=O)N1CCN(N)CC1.O=[N+]([O-])c1ccc(F)cc1
CC(C)(C)OC(=O)N1CCC(Nc2ccc([N+](=O)[O-])cc2)CC1
null
null
CN1C(CCC1)=O
Heteroatom Alkylation and Arylation
OtherReaction
cc9b9901cf7bcaed21146ada6cf4db3f680b984a6f9db4384ca71eee47dcc6c5
955fdd0cb8b5627845dcae067e53d4eb8e2b1614a3423f9d92a540c8222ab38b
c1ccc(NC2CCNCC2)cc1
F-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5].[C;D1;H3:6]-[C:7](-[C;D1;H3:8])(-[C;D1;H3:9])-[#8:10]-[C:11](=[O;D1;H0:12])-[#7:13]1-[C:14]-[CH2;D2;+0:15]-N(-[NH2;D1;+0:16])-[CH2;D2;+0:17]-[C:18]-1>>[C;D1;H3:6]-[C:7](-[C;D1;H3:8])(-[C;D1;H3:9])-[#8:10]-[C:11](=[O;D1;H0:12])-[#7:13]1-[C:14]-[CH2;D2;+0:15]-[C:19](-[NH;D2;+0:1...
53.2
[{"value": 53.2, "product": "C(C)(C)(C)OC(=O)N1CCC(CC1)NC1=CC=C(C=C1)[N+](=O)[O-]", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
80
CELSIUS
18
HOUR
4-Amino-1-tert-butoxycarbonylpiperazine (3.00 g), 4-fluoronitrobenzene (2.54 g) and N,N-diisopropylethylamine (8.82 g) were dissolved in N-methyl-2-pyrrolidone (30 mL), and the mixture was stirred at 80° C. for 18 hr. The reaction mixture was added to water and the mixture was extracted with ethyl acetate. The extract ...
10.6084/m9.figshare.5104873.v1
null
Hydrazine.Aromatic halide
Secondary amine
C1CNCC[NH]1.c1ccccc1
C1CC[NH]CC1.c1ccccc1
C1CC[NH]CC1.c1ccccc1
Other
CN1C(CCC1)=O
80
18
CC(C)(C)OC(=O)N1CCN(N)CC1.O=[N+]([O-])c1ccc(F)cc1>CN1C(CCC1)=O>CC(C)(C)OC(=O)N1CCC(Nc2ccc([N+](=O)[O-])cc2)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-a7d395d8b4204e2f810e2e993877d9bd
C=O.CC(C)(C)OC(=O)N1C[C@@H](N2CCC(Nc3ccccc3)CC2)C[C@H]1C(=O)N1CCSC1>>CN(c1ccccc1)C1CCN([C@H]2C[C@@H](C(=O)N3CCSC3)N(C(=O)OC(C)(C)C)C2)CC1
N(C1=CC=CC=C1)C1CCN(CC1)[C@H]1C[C@H](N(C1)C(=O)OC(C)(C)C)C(=O)N1CSCC1.Cl.Cl.Cl.N(C1=CC=CC=C1)C1CCN(CC1)[C@H]1C[C@H](NC1)C(=O)N1CSCC1.C(C)(=O)O[BH-](OC(C)=O)OC(C)=O.[Na+].C=O>>C(C)(C)(C)OC(=O)N1[C@@H](C[C@@H](C1)N1CCC(CC1)N(C1=CC=CC=C1)C)C(=O)N1CSCC1
O=[CH2:1].[NH:2]([c:3]1[cH:4][cH:5][cH:6][cH:7][cH:8]1)[CH:9]1[CH2:10][CH2:11][N:12]([C@H:13]2[CH2:14][C@@H:15]([C:16](=[O:17])[N:18]3[CH2:19][CH2:20][S:21][CH2:22]3)[N:23]([C:24](=[O:25])[O:26][C:27]([CH3:28])([CH3:29])[CH3:30])[CH2:31]2)[CH2:32][CH2:33]1>>[CH3:1][N:2]([c:3]1[cH:4][cH:5][cH:6][cH:7][cH:8]1)[CH:9]1[CH2...
C=O.CC(C)(C)OC(=O)N1C[C@@H](N2CCC(Nc3ccccc3)CC2)C[C@H]1C(=O)N1CCSC1
CN(c1ccccc1)C1CCN([C@H]2C[C@@H](C(=O)N3CCSC3)N(C(=O)OC(C)(C)C)C2)CC1
null
null
C(C)(=O)O.ClCCCl.O
Heteroatom Alkylation and Arylation
Eschweiler-Clarke Secondary Amine Methylation
deb0f39510ff32c3bd75ceaf7ece4070b1f686ff120d798ccd640765025dab3c
e1fdef8fde1c506d7c9deb8fd5e6f322eceea2abce3167abcf412a1fa4fd5443
O=C([C@@H]1C[C@H](N2CCC(Nc3ccccc3)CC2)CN1)N1CCSC1
O=[CH2;D1;+0:1].[C:2]-[C:3](-[NH;D2;+0:4]-[c:5](:[c:6]):[c:7])-[C:8]>>[C:2]-[C:3](-[N;H0;D3;+0:4](-[CH3;D1;+0:1])-[c:5](:[c:6]):[c:7])-[C:8]
null
[]
null
null
12
HOUR
3-[(2S,4S)-4-(4-Anilinopiperidino)-1-tert-butoxycarbonyl-2-pyrrolidinylcarbonyl]-1,3-thiazolidine [product of Example 148 (3), 1.18 g] was dissolved in 1,2-dichloroethane (75 mL), and sodium triacetoxyborohydride (5.32 g), acetic acid (0.73 mL) and 37% formaldehyde solution (5.0 mL) were added thereto. The mixture was ...
10.6084/m9.figshare.5104873.v1
null
Formaldehyde.Secondary amine
Tertiary amine
null
null
c1ccccc1.C1CC[NH]CC1.C1CC[NH]C1.C1CSC[NH]1
Other
C(C)(=O)O.ClCCCl.O
null
12
C=O.CC(C)(C)OC(=O)N1C[C@@H](N2CCC(Nc3ccccc3)CC2)C[C@H]1C(=O)N1CCSC1>C(C)(=O)O.ClCCCl.O>CN(c1ccccc1)C1CCN([C@H]2C[C@@H](C(=O)N3CCSC3)N(C(=O)OC(C)(C)C)C2)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-83132976d59148e8bea04b988527ffdb
C1CC2(CCN1)OCCO2.O=[N+]([O-])c1ccc(F)cc1>>O=[N+]([O-])c1ccc(N2CCC3(CC2)OCCO3)cc1
O1CCOC12CCNCC2.C(C)(C)N(CC)C(C)C.FC1=CC=C(C=C1)[N+](=O)[O-]>>C1COC2(CCN(CC2)C2=CC=C(C=C2)[N+](=O)[O-])O1
[NH:8]1[CH2:9][CH2:10][C:11]2([CH2:12][CH2:13]1)[O:14][CH2:15][CH2:16][O:17]2.F[c:7]1[cH:6][cH:5][c:4]([N+:2](=[O:1])[O-:3])[cH:19][cH:18]1>>[O:1]=[N+:2]([O-:3])[c:4]1[cH:5][cH:6][c:7]([N:8]2[CH2:9][CH2:10][C:11]3([CH2:12][CH2:13]2)[O:14][CH2:15][CH2:16][O:17]3)[cH:18][cH:19]1
C1CC2(CCN1)OCCO2.O=[N+]([O-])c1ccc(F)cc1
O=[N+]([O-])c1ccc(N2CCC3(CC2)OCCO3)cc1
null
null
O
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation secondary amine
163ff2ee5dd6c15769cf883428ba870eed9db794603d1900dd68b8b7dc727535
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
c1ccc(N2CCC3(CC2)OCCO3)cc1
F-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5].[C:6]-[C:7]-[NH;D2;+0:8]-[C:9]-[C:10]>>[C:6]-[C:7]-[N;H0;D3;+0:8](-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5])-[C:9]-[C:10]
80.2
[{"value": 80.2, "product": "C1COC2(CCN(CC2)C2=CC=C(C=C2)[N+](=O)[O-])O1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
1,4-Dioxa-8-azaspiro[4,5]decane (7.88 g) was dissolved in N-methyl-2-pyrrolidine (50 mL), and diisopropylethylamine (9.5.8 mL) and 4-fluoronitrobenzene (7.06 g) were successively added. The mixture was stirred at room temperature for 2 hr. The reaction mixture was added to iced water, and the precipitated solid was col...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CC2(CCN1)OCCO2.c1ccccc1
c1ccccc1.C1CC2(CC[NH]1)OCCO2
c1ccccc1.C1CC2(CC[NH]1)OCCO2
HF
O
null
2
C1CC2(CCN1)OCCO2.O=[N+]([O-])c1ccc(F)cc1>O>O=[N+]([O-])c1ccc(N2CCC3(CC2)OCCO3)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-1ed59873ae734812b5b5a08a76fbb05e
CCN(C(C)C)C(C)C.N#Cc1ccc(CBr)cc1.O=C([C@@H]1C[C@H](NC2CCN(c3ccc([N+](=O)[O-])cc3)CC2)CN1)N1CCSC1>>CC(C)(C)OC(=O)N1C[C@@H](N(Cc2ccc(C#N)cc2)C2CCN(c3ccc([N+](=O)[O-])cc3)CC2)C[C@H]1C(=O)N1CCSC1
C(O)([O-])=O.[Na+].C(#N)C1=CC=C(CBr)C=C1.C(C)(C)N(CC)C(C)C.Cl.Cl.Cl.[N+](=O)([O-])C1=CC=C(C=C1)N1CCC(CC1)N[C@H]1C[C@H](NC1)C(=O)N1CSCC1.CN1C(CCC1)=O>>C(C)(C)(C)OC(=O)N1[C@@H](C[C@@H](C1)N(C1CCN(CC1)C1=CC=C(C=C1)[N+](=O)[O-])CC1=CC=C(C=C1)C#N)C(=O)N1CSCC1
CCN(C(C)[CH3:4])[CH:2]([CH3:1])[CH3:3].Br[CH2:12][c:13]1[cH:14][cH:15][c:16]([C:17]#[N:18])[cH:19][cH:20]1.[NH:8]1[CH2:9][C@@H:10]([NH:11][CH:21]2[CH2:22][CH2:23][N:24]([c:25]3[cH:26][cH:27][c:28]([N+:29](=[O:30])[O-:31])[cH:32][cH:33]3)[CH2:34][CH2:35]2)[CH2:36][C@H:37]1[C:38](=[O:39])[N:40]1[CH2:41][CH2:42][S:43][CH2...
CCN(C(C)C)C(C)C.N#Cc1ccc(CBr)cc1.O=C([C@@H]1C[C@H](NC2CCN(c3ccc([N+](=O)[O-])cc3)CC2)CN1)N1CCSC1
CC(C)(C)OC(=O)N1C[C@@H](N(Cc2ccc(C#N)cc2)C2CCN(c3ccc([N+](=O)[O-])cc3)CC2)C[C@H]1C(=O)N1CCSC1
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
d8a307254dc3bc6e195371883ab2dcb9c63e02e01e71116906b5082e7b8a3200
23d66b49c456aba6d2ef193a6aa42c9f8b3e98a106c32c8e4e3d9ccc98c1a74b
O=C([C@@H]1C[C@H](N(Cc2ccccc2)C2CCN(c3ccccc3)CC2)CN1)N1CCSC1
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].C-C-N(-C(-C)-[CH3;D1;+0:5])-[CH;D3;+0:6](-[C;D1;H3:7])-[C;D1;H3:8].[#16:9]-[C:10]-[#7:11](-[C:12](=[O;D1;H0:13])-[C:14]1-[C:15]-[C:16](-[NH;D2;+0:17]-[C:18](-[C:19])-[C:20])-[C:21]-[NH;D2;+0:22]-1)-[C:23]>>[#16:9]-[C:10]-[#7:11](-[C:12](=[O;D1;H0:13])-[C:14]1-[C:15]-[C:16](-[N;H0;D3...
null
[]
80
CELSIUS
8
HOUR
The product (1.01 g) of Example 156 (3) was dissolved in N-methyl-2-pyrrolidone (6 mL), and 4-cyanobenzyl bromide (0.392 g) and diisopropylethylamine (1.05 mL) were added thereto. The mixture was stirred at 80° C. for 8 hr with heating. The reaction mixture was added to saturated aqueous sodium hydrogencarbonate soluti...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amine.Secondary amine.Tertiary amine
Carbamic ester.Ether.Tertiary amine.Boc
C1CCNC1
C1CC[NH]C1
C1CC[NH]C1.c1ccccc1.C1CC[NH]CC1.c1ccccc1.C1CSC[NH]1
HBr
null
80
8
CCN(C(C)C)C(C)C.N#Cc1ccc(CBr)cc1.O=C([C@@H]1C[C@H](NC2CCN(c3ccc([N+](=O)[O-])cc3)CC2)CN1)N1CCSC1>>CC(C)(C)OC(=O)N1C[C@@H](N(Cc2ccc(C#N)cc2)C2CCN(c3ccc([N+](=O)[O-])cc3)CC2)C[C@H]1C(=O)N1CCSC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-204c7715386d4076acd8efd08ea4eaac
C1CNCCN1.O=[N+]([O-])c1ccccc1F>>O=[N+]([O-])c1ccccc1N1CCNCC1
N1CCNCC1.FC1=C(C=CC=C1)[N+](=O)[O-].O>>[N+](=O)([O-])C1=C(C=CC=C1)N1CCNCC1
[NH:10]1[CH2:11][CH2:12][NH:13][CH2:14][CH2:15]1.F[c:9]1[c:4]([N+:2](=[O:1])[O-:3])[cH:5][cH:6][cH:7][cH:8]1>>[O:1]=[N+:2]([O-:3])[c:4]1[cH:5][cH:6][cH:7][cH:8][c:9]1[N:10]1[CH2:11][CH2:12][NH:13][CH2:14][CH2:15]1
C1CNCCN1.O=[N+]([O-])c1ccccc1F
O=[N+]([O-])c1ccccc1N1CCNCC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation secondary amine
1d452876efa46787ecd5eab4acf018720843b51fbe40244616ffd72f6a602335
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
c1ccc(N2CCNCC2)cc1
F-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[#7;+:5]):[c:6].[#7:7]1-[C:8]-[C:9]-[NH;D2;+0:10]-[C:11]-[C:12]-1>>[#7;+:5]-[c:4](:[c:6]):[c;H0;D3;+0:1](-[N;H0;D3;+0:10]1-[C:9]-[C:8]-[#7:7]-[C:12]-[C:11]-1):[c:2]:[c:3]
74.3
[{"value": 74.3, "product": "[N+](=O)([O-])C1=C(C=CC=C1)N1CCNCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3
HOUR
Piperazine (12.9 g) was dissolved in DMF (100 mL), and a solution of 2-fluoronitrobenzene (7.06 g) in DMF (30 mL) was added dropwise. The mixture was stirred at room temperature for 3 hr. The reaction mixture was added to water and the mixture was extracted with ethyl acetate. The extract was washed with water and drie...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CNCCN1.c1ccccc1
c1ccccc1.C1C[NH]CCN1
c1ccccc1.C1C[NH]CCN1
HF
CN(C)C=O
null
3
C1CNCCN1.O=[N+]([O-])c1ccccc1F>CN(C)C=O>O=[N+]([O-])c1ccccc1N1CCNCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-330decb74c1641509158bc72bf2d1e53
C1CNCCN1.FC(F)(F)c1ccc(Cl)nc1>>FC(F)(F)c1ccc(N2CCNCC2)nc1
N1CCNCC1.ClC1=NC=C(C=C1)C(F)(F)F.O>>FC(C=1C=CC(=NC1)N1CCNCC1)(F)F
[NH:9]1[CH2:10][CH2:11][NH:12][CH2:13][CH2:14]1.Cl[c:8]1[cH:7][cH:6][c:5]([C:2]([F:1])([F:3])[F:4])[cH:16][n:15]1>>[F:1][C:2]([F:3])([F:4])[c:5]1[cH:6][cH:7][c:8]([N:9]2[CH2:10][CH2:11][NH:12][CH2:13][CH2:14]2)[n:15][cH:16]1
C1CNCCN1.FC(F)(F)c1ccc(Cl)nc1
FC(F)(F)c1ccc(N2CCNCC2)nc1
null
null
CN1C(CCC1)=O
Heteroatom Alkylation and Arylation
Ullmann-Goldberg Substitution amine
2cfe79e260e5807469ed13cb0f911e98374b23b23e32c97becca8eb2afcb1c66
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
c1ccc(N2CCNCC2)nc1
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[c:4]:[c:5].[#7:6]1-[C:7]-[C:8]-[NH;D2;+0:9]-[C:10]-[C:11]-1>>[c:3]:[#7;a:2]:[c;H0;D3;+0:1](-[N;H0;D3;+0:9]1-[C:8]-[C:7]-[#7:6]-[C:11]-[C:10]-1):[c:4]:[c:5]
99.4
[{"value": 99.4, "product": "FC(C=1C=CC(=NC1)N1CCNCC1)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
18
HOUR
Piperazine (12.9 g) was suspended in N-methyl-2-pyrrolidone (130 mL), and a solution of 2-chloro-5-trifluoromethylpyridine (9.08 g) in N-methyl-2-pyrrolidone (30 mL) was added dropwise. The mixture was stirred at room temperature for 18 hr. The reaction mixture was added to water and the mixture was extracted with ethy...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CNCCN1.c1ccncc1
c1ccncc1.C1C[NH]CCN1
c1ccncc1.C1C[NH]CCN1
HCl
CN1C(CCC1)=O
null
18
C1CNCCN1.FC(F)(F)c1ccc(Cl)nc1>CN1C(CCC1)=O>FC(F)(F)c1ccc(N2CCNCC2)nc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-2ede453e32e24a7c87809f58521e105c
C1CNCCN1.Clc1ccnc2ccccc12>>c1ccc2c(N3CCNCC3)ccnc2c1
N1CCNCC1.ClC1=CC=NC2=CC=CC=C12>>N1=CC=C(C2=CC=CC=C12)N1CCNCC1
[NH:6]1[CH2:7][CH2:8][NH:9][CH2:10][CH2:11]1.Cl[c:5]1[c:4]2[cH:3][cH:2][cH:1][cH:16][c:15]2[n:14][cH:13][cH:12]1>>[cH:1]1[cH:2][cH:3][c:4]2[c:5]([N:6]3[CH2:7][CH2:8][NH:9][CH2:10][CH2:11]3)[cH:12][cH:13][n:14][c:15]2[cH:16]1
C1CNCCN1.Clc1ccnc2ccccc12
c1ccc2c(N3CCNCC3)ccnc2c1
null
null
O
Heteroatom Alkylation and Arylation
Ullmann-Goldberg Substitution amine
3fbb016f359467d4eec60eb9e91655d372a48980ac0112856b33886c38619450
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
c1ccc2c(N3CCNCC3)ccnc2c1
Cl-[c;H0;D3;+0:1]1:[c:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#7:9]1-[C:10]-[C:11]-[NH;D2;+0:12]-[C:13]-[C:14]-1>>[c:6]:[c:5]1:[#7;a:4]:[c:3]:[c:2]:[c;H0;D3;+0:1](-[N;H0;D3;+0:12]2-[C:11]-[C:10]-[#7:9]-[C:14]-[C:13]-2):[c:7]:1:[c:8]
105.9
[{"value": 105.9, "product": "N1=CC=C(C2=CC=CC=C12)N1CCNCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
140
CELSIUS
30
MINUTE
Piperazine (13.2 g) was melted by heating at 140° C., and 4-chloroquinoline (2.5 g) was added thereto. The mixture was stirred at 140° C. for 30 min. The reaction mixture was added to iced water, and the mixture was extracted with chloroform to give 1-(4-quinolyl)piperazine (3.45 g) as a pale-yellow oil. Conditions: Se...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CNCCN1.c1ccc2ncccc2c1
C1C[NH]CCN1.c1ccc2ncccc2c1
C1C[NH]CCN1.c1ccc2ncccc2c1
HCl
O
140
0.5
C1CNCCN1.Clc1ccnc2ccccc12>O>c1ccc2c(N3CCNCC3)ccnc2c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-8b054729c25147f6b59e545e209052b6
CC(C)(C)OC(=O)N1CCNCC1.O=S(=O)(Cl)c1cccc2cccnc12>>O=S(=O)(c1cccc2cccnc12)N1CCNCC1
C(CC(O)(C(=O)O)CC(=O)O)(=O)O.C(C)(C)(C)OC(=O)N1CCNCC1.C(C)N(CC)CC.N1=CC=CC2=CC=CC(=C12)S(=O)(=O)Cl>>N1=CC=CC2=CC=CC(=C12)S(=O)(=O)N1CCNCC1
CC(C)(C)OC(=O)[N:14]1[CH2:15][CH2:16][NH:17][CH2:18][CH2:19]1.Cl[S:2](=[O:1])(=[O:3])[c:4]1[cH:5][cH:6][cH:7][c:8]2[cH:9][cH:10][cH:11][n:12][c:13]12>>[O:1]=[S:2](=[O:3])([c:4]1[cH:5][cH:6][cH:7][c:8]2[cH:9][cH:10][cH:11][n:12][c:13]12)[N:14]1[CH2:15][CH2:16][NH:17][CH2:18][CH2:19]1
CC(C)(C)OC(=O)N1CCNCC1.O=S(=O)(Cl)c1cccc2cccnc12
O=S(=O)(c1cccc2cccnc12)N1CCNCC1
null
null
ClCCl
Acylation
OtherReaction
fe80f4ba0030540fe0dd5c07c99df28cb9dc1f06dbe0a7382338f606945d5f85
705725ff5b1b5bdebe12db390e8895152ae89941b9a07e00716e981f5b25c654
O=S(=O)(c1cccc2cccnc12)N1CCNCC1
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1]1-[C:2]-[C:3]-[#7:4]-[C:5]-[C:6]-1.Cl-[S;H0;D4;+0:7](=[O;D1;H0:8])(=[O;D1;H0:9])-[c:10](:[c:11]):[c:12](:[c:13]):[#7;a:14]:[c:15]>>[O;D1;H0:8]=[S;H0;D4;+0:7](=[O;D1;H0:9])(-[N;H0;D3;+0:1]1-[C:2]-[C:3]-[#7:4]-[C:5]-[C:6]-1)-[c:10](:[c:11]):[c:12](:[c:13]):[#7;a:14]:[c:15]
22.1
[{"value": 22.1, "product": "N1=CC=CC2=CC=CC(=C12)S(=O)(=O)N1CCNCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
14
HOUR
1-tert-Butoxycarbonylpiperazine (2.22 g) and triethylamine (2.0 mL) were dissolved in dichloromethane (100 mL), and 8-quinolinesulfonyl chloride (2.71 g) was added thereto. The mixture was stirred at room temperature for 14 hr. 10% citric acid solution was added to the reaction mixture and the mixture was extracted wit...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Sulfonyl halide.Boc
Tertiary amine
C1C[NH]CCN1
C1C[NH]CCN1
c1ccc2ncccc2c1.C1C[NH]CCN1
HCl
ClCCl
null
14
CC(C)(C)OC(=O)N1CCNCC1.O=S(=O)(Cl)c1cccc2cccnc12>ClCCl>O=S(=O)(c1cccc2cccnc12)N1CCNCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-8bbdd2e30e644bb99b1cbacfcc867298
C1CNCCN1.N#Cc1cccnc1Cl>>N#Cc1cccnc1N1CCNCC1
N1CCNCC1.ClC1=NC=CC=C1C#N>>C(#N)C=1C(=NC=CC1)N1CCNCC1
[NH:9]1[CH2:10][CH2:11][NH:12][CH2:13][CH2:14]1.Cl[c:8]1[c:3]([C:2]#[N:1])[cH:4][cH:5][cH:6][n:7]1>>[N:1]#[C:2][c:3]1[cH:4][cH:5][cH:6][n:7][c:8]1[N:9]1[CH2:10][CH2:11][NH:12][CH2:13][CH2:14]1
C1CNCCN1.N#Cc1cccnc1Cl
N#Cc1cccnc1N1CCNCC1
null
null
O
Heteroatom Alkylation and Arylation
Ullmann-Goldberg Substitution amine
2cfe79e260e5807469ed13cb0f911e98374b23b23e32c97becca8eb2afcb1c66
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
c1ccc(N2CCNCC2)nc1
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[c:4](-[C:5]#[N;D1;H0:6]):[c:7].[#7:8]1-[C:9]-[C:10]-[NH;D2;+0:11]-[C:12]-[C:13]-1>>[N;D1;H0:6]#[C:5]-[c:4](:[c:7]):[c;H0;D3;+0:1](-[N;H0;D3;+0:11]1-[C:10]-[C:9]-[#7:8]-[C:13]-[C:12]-1):[#7;a:2]:[c:3]
89.1
[{"value": 89.1, "product": "C(#N)C=1C(=NC=CC1)N1CCNCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
150
CELSIUS
2
HOUR
Piperazine (125 g) was melted by heating at 150° C. and 2-chloro-3-cyanopyridine (20.0 g) was added thereto. The mixture was stirred at 110° C. for 2 hr. Water was added to the reaction mixture and the mixture was extracted with chloroform. The extract was washed with brine, dried and concentrated under reduced pressur...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CNCCN1.c1ccncc1
c1ccncc1.C1C[NH]CCN1
c1ccncc1.C1C[NH]CCN1
HCl
O
150
2
C1CNCCN1.N#Cc1cccnc1Cl>O>N#Cc1cccnc1N1CCNCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-0e222f2b038a4783a0650a01c212fb9d
C1CNCCN1.Clc1cccnc1Cl>>Clc1cccnc1N1CCNCC1
N1CCNCC1.ClC1=NC=CC=C1Cl>>ClC=1C(=NC=CC1)N1CCNCC1
[NH:8]1[CH2:9][CH2:10][NH:11][CH2:12][CH2:13]1.Cl[c:7]1[c:2]([Cl:1])[cH:3][cH:4][cH:5][n:6]1>>[Cl:1][c:2]1[cH:3][cH:4][cH:5][n:6][c:7]1[N:8]1[CH2:9][CH2:10][NH:11][CH2:12][CH2:13]1
C1CNCCN1.Clc1cccnc1Cl
Clc1cccnc1N1CCNCC1
null
null
O
Heteroatom Alkylation and Arylation
Ullmann-Goldberg Substitution amine
2cfe79e260e5807469ed13cb0f911e98374b23b23e32c97becca8eb2afcb1c66
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
c1ccc(N2CCNCC2)nc1
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[c:4](-[Cl;D1;H0:5]):[c:6].[#7:7]1-[C:8]-[C:9]-[NH;D2;+0:10]-[C:11]-[C:12]-1>>[Cl;D1;H0:5]-[c:4](:[c:6]):[c;H0;D3;+0:1](-[N;H0;D3;+0:10]1-[C:11]-[C:12]-[#7:7]-[C:8]-[C:9]-1):[#7;a:2]:[c:3]
102.5
[{"value": 102.5, "product": "ClC=1C(=NC=CC1)N1CCNCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
140
CELSIUS
2
HOUR
Piperazine (20.0 g) was melted by heating at 140° C. and 2,3-dichloropyridine (3.42 g) was added thereto. The mixture was stirred at 120° C. for 2 hr. Water was added to the reaction mixture and the mixture was extracted with chloroform. The extract was washed with brine, dried and concentrated under reduced pressure t...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CNCCN1.c1ccncc1
c1ccncc1.C1C[NH]CCN1
c1ccncc1.C1C[NH]CCN1
HCl
O
140
2
C1CNCCN1.Clc1cccnc1Cl>O>Clc1cccnc1N1CCNCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-69c0cd41b4cf4561add0bc2143501f5e
CC(C)(C)OC(=O)N1CCNCC1.CCOC(=O)c1ccc(Cl)nc1>>CCOC(=O)c1ccc(N2CCNCC2)nc1
O.C(C)(C)(C)OC(=O)N1CCNCC1.C([O-])([O-])=O.[K+].[K+].ClC1=NC=C(C(=O)OCC)C=C1>>C(C)OC(=O)C=1C=CC(=NC1)N1CCNCC1
CC(C)(C)OC(=O)[N:13]1[CH2:12][CH2:11][NH:10][CH2:15][CH2:14]1.Cl[c:9]1[cH:8][cH:7][c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[cH:17][n:16]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][cH:8][c:9]([N:10]2[CH2:11][CH2:12][NH:13][CH2:14][CH2:15]2)[n:16][cH:17]1
CC(C)(C)OC(=O)N1CCNCC1.CCOC(=O)c1ccc(Cl)nc1
CCOC(=O)c1ccc(N2CCNCC2)nc1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
OtherReaction
f9ec877b49b3a228c02d63b268ec6a17dab199dccd6d2eaf006bf52df974c50d
4692e9cfac8ca0f49eb5c33838ae1fa5c1a375a44556f0da8885d569da661aa1
c1ccc(N2CCNCC2)nc1
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1]1-[C:2]-[C:3]-[NH;D2;+0:4]-[C:5]-[C:6]-1.Cl-[c;H0;D3;+0:7](:[#7;a:8]:[c:9]):[c:10]:[c:11]>>[c:9]:[#7;a:8]:[c;H0;D3;+0:7](-[N;H0;D3;+0:4]1-[C:3]-[C:2]-[NH;D2;+0:1]-[C:6]-[C:5]-1):[c:10]:[c:11]
82.4
[{"value": 82.4, "product": "C(C)OC(=O)C=1C=CC(=NC1)N1CCNCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
80
CELSIUS
18
HOUR
Ethyl 6-chloronicotinate (1.12 g) was dissolved in DMF (30 mL), and 1-tert-butoxycarbonylpiperazine (1.24 g) and potassium carbonate (1.00 g) were added thereto. The mixture was stirred at 80° C. for 18 hr. Water (100 mL) was added to the reaction mixture and the mixture was extracted with ethyl acetate. The extract wa...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Carbamic ester.Ether.Secondary amine.Boc
Secondary amine.Tertiary amine
C1C[NH]CCN1.c1ccncc1
c1ccncc1.C1C[NH]CCN1
c1ccncc1.C1C[NH]CCN1
HCl
CN(C)C=O
80
18
CC(C)(C)OC(=O)N1CCNCC1.CCOC(=O)c1ccc(Cl)nc1>CN(C)C=O>CCOC(=O)c1ccc(N2CCNCC2)nc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-848321933638496791a905e67270be84
CCOC(=O)c1ccc(N2CCN([C@@H]3CN[C@H](C(=O)N4CCSC4)C3)CC2)nc1.Cl>>Cl.O=C(O)c1ccc(N2CCN([C@@H]3CN[C@H](C(=O)N4CCSC4)C3)CC2)nc1
Cl.Cl.Cl.Cl.C(C)(C)(C)OC(=O)N1[C@@H](C[C@@H](C1)N1CCN(CC1)C1=NC=C(C=C1)C(=O)OCC)C(=O)N1CSCC1.Cl.Cl.Cl.C(C)OC(=O)C=1C=CC(=NC1)N1CCN(CC1)[C@H]1C[C@H](NC1)C(=O)N1CSCC1>>Cl.Cl.Cl.C(=O)(O)C=1C=CC(=NC1)N1CCN(CC1)[C@H]1C[C@H](NC1)C(=O)N1CSCC1
CC[O:6][C:5](=[O:4])[c:7]1[cH:8][cH:9][c:10]([N:11]2[CH2:12][CH2:13][N:14]([C@@H:15]3[CH2:16][NH:17][C@H:18]([C:19](=[O:20])[N:21]4[CH2:22][CH2:23][S:24][CH2:25]4)[CH2:26]3)[CH2:27][CH2:28]2)[n:29][cH:30]1.[ClH:3]>>[ClH:3].[O:4]=[C:5]([OH:6])[c:7]1[cH:8][cH:9][c:10]([N:11]2[CH2:12][CH2:13][N:14]([C@@H:15]3[CH2:16][NH:1...
CCOC(=O)c1ccc(N2CCN([C@@H]3CN[C@H](C(=O)N4CCSC4)C3)CC2)nc1.Cl
Cl.O=C(O)c1ccc(N2CCN([C@@H]3CN[C@H](C(=O)N4CCSC4)C3)CC2)nc1
null
null
null
Miscellaneous
OtherReaction
16eb0e22715fadede32e44259800ac2375ae7dbc609f9ec677d59917bae07bec
b51da43dbb7140dac708518f8dbf83c5b067214819134afdb3f427285d08d6f8
O=C([C@@H]1C[C@H](N2CCN(c3ccccn3)CC2)CN1)N1CCSC1
C-C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]:[c:5]:[#7;a:6]>>[#7;a:6]:[c:5]:[c:4]-[C:2](=[O;D1;H0:3])-[OH;D1;+0:1]
null
[]
null
null
null
null
6 mol/L Hydrochloric acid was added to 3-{(2S,4S)-1-tert-butoxycarbonyl-4-[4-(5-ethoxycarbonyl-2-pyridyl)-1-piperazinyl]-2-pyrrolidinylcarbonyl}-1,3-thiazolidine trihydrochloride [product of Example 211 (2), 1.00 g] and the mixture was refluxed for 2 hr. The solvent was evaporated under reduced pressure, and the residu...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccncc1.C1C[NH]CC[NH]1.C1CCNC1.C1CSC[NH]1
Other
null
null
null
CCOC(=O)c1ccc(N2CCN([C@@H]3CN[C@H](C(=O)N4CCSC4)C3)CC2)nc1.Cl>>Cl.O=C(O)c1ccc(N2CCN([C@@H]3CN[C@H](C(=O)N4CCSC4)C3)CC2)nc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-4d07e9a838ac401f84a0d0ffd1310bb7
C1CNCCN1.NC(=O)c1ccc(Cl)nc1>>NC(=O)c1ccc(N2CCNCC2)nc1
ClC1=NC=C(C(=O)N)C=C1.N1CCNCC1>>C(N)(=O)C=1C=CC(=NC1)N1CCNCC1
[NH:8]1[CH2:9][CH2:10][NH:11][CH2:12][CH2:13]1.Cl[c:7]1[cH:6][cH:5][c:4]([C:2]([NH2:1])=[O:3])[cH:15][n:14]1>>[NH2:1][C:2](=[O:3])[c:4]1[cH:5][cH:6][c:7]([N:8]2[CH2:9][CH2:10][NH:11][CH2:12][CH2:13]2)[n:14][cH:15]1
C1CNCCN1.NC(=O)c1ccc(Cl)nc1
NC(=O)c1ccc(N2CCNCC2)nc1
null
null
null
Heteroatom Alkylation and Arylation
Ullmann-Goldberg Substitution amine
2cfe79e260e5807469ed13cb0f911e98374b23b23e32c97becca8eb2afcb1c66
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
c1ccc(N2CCNCC2)nc1
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[c:4]:[c:5].[#7:6]1-[C:7]-[C:8]-[NH;D2;+0:9]-[C:10]-[C:11]-1>>[c:3]:[#7;a:2]:[c;H0;D3;+0:1](-[N;H0;D3;+0:9]1-[C:10]-[C:11]-[#7:6]-[C:7]-[C:8]-1):[c:4]:[c:5]
6.2
[{"value": 6.2, "product": "C(N)(=O)C=1C=CC(=NC1)N1CCNCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using 6-chloronicotinamide (5.00 g) and piperazine (27.6 g), and by reaction in the same manner as in Example 196 (1) at 100° C., 1-(5-carbamoyl-2-pyridyl)piperazine (0.41 g) was obtained as a yellow powder. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CNCCN1.c1ccncc1
c1ccncc1.C1C[NH]CCN1
c1ccncc1.C1C[NH]CCN1
HCl
null
null
null
C1CNCCN1.NC(=O)c1ccc(Cl)nc1>>NC(=O)c1ccc(N2CCNCC2)nc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-898e10ec32214655b9bc6942c0a9890c
C1CNCCN1.FC(F)(F)c1cnc(Cl)c(Cl)c1>>FC(F)(F)c1cnc(N2CCNCC2)c(Cl)c1
N1CCNCC1.ClC1=NC=C(C=C1Cl)C(F)(F)F>>ClC=1C(=NC=C(C1)C(F)(F)F)N1CCNCC1
[NH:9]1[CH2:10][CH2:11][NH:12][CH2:13][CH2:14]1.Cl[c:8]1[n:7][cH:6][c:5]([C:2]([F:1])([F:3])[F:4])[cH:17][c:15]1[Cl:16]>>[F:1][C:2]([F:3])([F:4])[c:5]1[cH:6][n:7][c:8]([N:9]2[CH2:10][CH2:11][NH:12][CH2:13][CH2:14]2)[c:15]([Cl:16])[cH:17]1
C1CNCCN1.FC(F)(F)c1cnc(Cl)c(Cl)c1
FC(F)(F)c1cnc(N2CCNCC2)c(Cl)c1
null
null
O
Heteroatom Alkylation and Arylation
Ullmann-Goldberg Substitution amine
2cfe79e260e5807469ed13cb0f911e98374b23b23e32c97becca8eb2afcb1c66
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
c1ccc(N2CCNCC2)nc1
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[c:4](-[Cl;D1;H0:5]):[c:6].[#7:7]1-[C:8]-[C:9]-[NH;D2;+0:10]-[C:11]-[C:12]-1>>[Cl;D1;H0:5]-[c:4](:[c:6]):[c;H0;D3;+0:1](-[N;H0;D3;+0:10]1-[C:9]-[C:8]-[#7:7]-[C:12]-[C:11]-1):[#7;a:2]:[c:3]
104.1
[{"value": 104.1, "product": "ClC=1C(=NC=C(C1)C(F)(F)F)N1CCNCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
140
CELSIUS
2
HOUR
Piperazine (40 g) was melted by heating at 140° C. and 2,3-dichloro-5-trifluoromethylpyridine (10 g) was added thereto. The mixture was stirred at 120° C. for 2 hr. Water was added to the reaction mixture and the mixture was extracted with chloroform. The extract was washed with brine, dried and concentrated under redu...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CNCCN1.c1ccncc1
c1ccncc1.C1C[NH]CCN1
c1ccncc1.C1C[NH]CCN1
HCl
O
140
2
C1CNCCN1.FC(F)(F)c1cnc(Cl)c(Cl)c1>O>FC(F)(F)c1cnc(N2CCNCC2)c(Cl)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-cca9370459ad44c084ce39b7dbc25385
CCO.O=C(O)c1cnc(Cl)c(Cl)c1>>CCOC(=O)c1cnc(Cl)c(Cl)c1
ClC=1C(=NC=C(C(=O)O)C1)Cl.C(C)O.S(=O)(Cl)Cl>>ClC=1C(=NC=C(C(=O)OCC)C1)Cl
[CH3:1][CH2:2][OH:3].O[C:4](=[O:5])[c:6]1[cH:7][n:8][c:9]([Cl:10])[c:11]([Cl:12])[cH:13]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][n:8][c:9]([Cl:10])[c:11]([Cl:12])[cH:13]1
CCO.O=C(O)c1cnc(Cl)c(Cl)c1
CCOC(=O)c1cnc(Cl)c(Cl)c1
null
null
null
Protection
Esterification of Carboxylic Acids
070670f68a20c1021da94fabee54def4688122fb721af5f52cd5a03630845d0e
0d8a72b7375d91aa7263e766e03a3cb7c4fa91e27abcd590409ff03b98eed690
c1ccncc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]:[#7;a:6]:[c:7].[C;D1;H3:8]-[C:9]-[OH;D1;+0:10]>>[C;D1;H3:8]-[C:9]-[O;H0;D2;+0:10]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]:[#7;a:6]:[c:7]
null
[]
null
null
null
null
5,6-Dichloronicotinic acid (4.90 g) was dissolved in ethanol (40 mL), and thionyl chloride (2.0 mL) was added thereto under ice-cooling. The mixture was refluxed for 1.5 hr. The reaction mixture was concentrated under reduced pressure, and saturated aqueous sodium hydrogencarbonate solution was added to the residue. Th...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary alcohol
Ester
null
null
c1ccncc1
HO-
null
null
null
CCO.O=C(O)c1cnc(Cl)c(Cl)c1>>CCOC(=O)c1cnc(Cl)c(Cl)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-fe7f0f39209c476a8500b303e5d04434
CCOC(=O)c1cnc(N2CCN([C@H]3C[C@@H](C(=O)N4CCSC4)N(C(=O)OC(C)(C)C)C3)CC2)c(Cl)c1>>CC(C)(C)OC(=O)N1C[C@@H](N2CCN(c3ncc(C(=O)O)cc3Cl)CC2)C[C@H]1C(=O)N1CCSC1
C(C)(C)(C)OC(=O)N1[C@@H](C[C@@H](C1)N1CCN(CC1)C1=NC=C(C=C1Cl)C(=O)OCC)C(=O)N1CSCC1.Cl.Cl.Cl.ClC=1C(=NC=C(C1)C(=O)OCC)N1CCN(CC1)[C@H]1C[C@H](NC1)C(=O)N1CSCC1.[OH-].[Li+]>>C(C)(C)(C)OC(=O)N1[C@@H](C[C@@H](C1)N1CCN(CC1)C1=NC=C(C=C1Cl)C(=O)O)C(=O)N1CSCC1
CC[O:21][C:19]([c:18]1[cH:17][n:16][c:15]([N:14]2[CH2:13][CH2:12][N:11]([C@@H:10]3[CH2:9][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[C@H:28]([C:29](=[O:30])[N:31]4[CH2:32][CH2:33][S:34][CH2:35]4)[CH2:27]3)[CH2:26][CH2:25]2)[c:23]([Cl:24])[cH:22]1)=[O:20]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8...
CCOC(=O)c1cnc(N2CCN([C@H]3C[C@@H](C(=O)N4CCSC4)N(C(=O)OC(C)(C)C)C3)CC2)c(Cl)c1
CC(C)(C)OC(=O)N1C[C@@H](N2CCN(c3ncc(C(=O)O)cc3Cl)CC2)C[C@H]1C(=O)N1CCSC1
null
null
C(C)O
Deprotection
Ester saponification (alkyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=C([C@@H]1C[C@H](N2CCN(c3ccccn3)CC2)CN1)N1CCSC1
C-C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]:[c:5]:[#7;a:6]>>[#7;a:6]:[c:5]:[c:4]-[C:2](=[O;D1;H0:3])-[OH;D1;+0:1]
42.8
[{"value": 42.8, "product": "C(C)(C)(C)OC(=O)N1[C@@H](C[C@@H](C1)N1CCN(CC1)C1=NC=C(C=C1Cl)C(=O)O)C(=O)N1CSCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
19
HOUR
3-{(2S,4S)-1-tert-Butoxycarbonyl-4-[4-(3-chloro-5-ethoxycarbonyl-2-pyridyl)-1-piperazinyl]-2-pyrrolidinylcarbonyl}-1,3-thiazolidine [product of Example 216 (3), 6.49 g] was dissolved in ethanol (30 mL), and aqueous solution (30 mL) of lithium hydroxide (0.59 g) was added thereto. The mixture was stirred at room tempera...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
C1CC[NH]C1.C1C[NH]CC[NH]1.c1ccncc1.C1CSC[NH]1
Other
C(C)O
null
19
CCOC(=O)c1cnc(N2CCN([C@H]3C[C@@H](C(=O)N4CCSC4)N(C(=O)OC(C)(C)C)C3)CC2)c(Cl)c1>C(C)O>CC(C)(C)OC(=O)N1C[C@@H](N2CCN(c3ncc(C(=O)O)cc3Cl)CC2)C[C@H]1C(=O)N1CCSC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-e6feafa42ea546d59bfe96bfbd63e1fb
CC(C)(C)OC(=O)N1C[C@@H](N2CCN(c3ncc(C(=O)O)cc3Cl)CC2)C[C@H]1C(=O)N1CCSC1.[NH4+]>>CC(C)(C)OC(=O)N1C[C@@H](N2CCN(c3ncc(C(N)=O)cc3Cl)CC2)C[C@H]1C(=O)N1CCSC1
C(C)(C)(C)OC(=O)N1[C@@H](C[C@@H](C1)N1CCN(CC1)C1=NC=C(C=C1Cl)C(=O)O)C(=O)N1CSCC1.Cl.Cl.Cl.C(=O)(O)C=1C=C(C(=NC1)N1CCN(CC1)[C@H]1C[C@H](NC1)C(=O)N1CSCC1)Cl.[Cl-].[NH4+].CN1CCOCC1.C=1C=CC2=C(C1)N=NN2O.CCN=C=NCCCN(C)C.Cl>>C(C)(C)(C)OC(=O)N1[C@@H](C[C@@H](C1)N1CCN(CC1)C1=NC=C(C=C1Cl)C(N)=O)C(=O)N1CSCC1
O[C:19]([c:18]1[cH:17][n:16][c:15]([N:14]2[CH2:13][CH2:12][N:11]([C@@H:10]3[CH2:9][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[C@H:28]([C:29](=[O:30])[N:31]4[CH2:32][CH2:33][S:34][CH2:35]4)[CH2:27]3)[CH2:26][CH2:25]2)[c:23]([Cl:24])[cH:22]1)=[O:21].[NH4+:20]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[...
CC(C)(C)OC(=O)N1C[C@@H](N2CCN(c3ncc(C(=O)O)cc3Cl)CC2)C[C@H]1C(=O)N1CCSC1.[NH4+]
CC(C)(C)OC(=O)N1C[C@@H](N2CCN(c3ncc(C(N)=O)cc3Cl)CC2)C[C@H]1C(=O)N1CCSC1
null
null
CN(C)C=O
Acylation
Carboxylic acid to amide conversion
1283aef55d7ee699f097a8e5267689198c76ba671644401547f902657820236d
cb0a71c3fb37a76e96fbd81aae6f95a28398a03d1ad2c8e877085e735efb98f1
O=C([C@@H]1C[C@H](N2CCN(c3ccccn3)CC2)CN1)N1CCSC1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]:[#7;a:6]:[c:7].[NH4+;D0:8]>>[NH2;D1;+0:8]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]:[#7;a:6]:[c:7]
null
[]
null
null
4
HOUR
3-{(2S,4S)-1-tert-Butoxycarbonyl-4-[4-(5-carboxy-3-chloro-2-pyridyl)-1-piperazinyl]-2-pyrrolidinylcarbonyl}-1,3-thiazolidine [product of Example 217 (1), 2.63 g] and ammonium chloride (0.54 g) were dissolved in DMF (30 mL), and N-methylmorpholine (1.1 mL), HOBT (1.53 g) and EDC hydrochloride (1.15 g) were successively ...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid
Primary amide
null
null
C1CC[NH]C1.C1C[NH]CC[NH]1.c1ccncc1.C1CSC[NH]1
HO-
CN(C)C=O
null
4
CC(C)(C)OC(=O)N1C[C@@H](N2CCN(c3ncc(C(=O)O)cc3Cl)CC2)C[C@H]1C(=O)N1CCSC1.[NH4+]>CN(C)C=O>CC(C)(C)OC(=O)N1C[C@@H](N2CCN(c3ncc(C(N)=O)cc3Cl)CC2)C[C@H]1C(=O)N1CCSC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-12a1736fbd544a5eb37ab329d42b0b4e
C1CNCCN1.Clc1cnc(Cl)c(Cl)c1>>Clc1cnc(N2CCNCC2)c(Cl)c1
N1CCNCC1.ClC1=NC=C(C=C1Cl)Cl>>ClC=1C(=NC=C(C1)Cl)N1CCNCC1
[NH:6]1[CH2:7][CH2:8][NH:9][CH2:10][CH2:11]1.Cl[c:5]1[n:4][cH:3][c:2]([Cl:1])[cH:14][c:12]1[Cl:13]>>[Cl:1][c:2]1[cH:3][n:4][c:5]([N:6]2[CH2:7][CH2:8][NH:9][CH2:10][CH2:11]2)[c:12]([Cl:13])[cH:14]1
C1CNCCN1.Clc1cnc(Cl)c(Cl)c1
Clc1cnc(N2CCNCC2)c(Cl)c1
null
null
O
Heteroatom Alkylation and Arylation
Ullmann-Goldberg Substitution amine
2cfe79e260e5807469ed13cb0f911e98374b23b23e32c97becca8eb2afcb1c66
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
c1ccc(N2CCNCC2)nc1
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[c:4](-[Cl;D1;H0:5]):[c:6].[#7:7]1-[C:8]-[C:9]-[NH;D2;+0:10]-[C:11]-[C:12]-1>>[Cl;D1;H0:5]-[c:4](:[c:6]):[c;H0;D3;+0:1](-[N;H0;D3;+0:10]1-[C:9]-[C:8]-[#7:7]-[C:12]-[C:11]-1):[#7;a:2]:[c:3]
101.1
[{"value": 101.1, "product": "ClC=1C(=NC=C(C1)Cl)N1CCNCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
140
CELSIUS
2
HOUR
Piperazine (24.0 g) was melted by heating at 140° C. and 2,3,5-trichloropyridine (5.00 g) was added thereto. The mixture was stirred at 120° C. for 2 hr. Water was added to the reaction mixture and the mixture was extracted with chloroform. The extract was washed with brine, dried and concentrated under reduced pressur...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CNCCN1.c1ccncc1
c1ccncc1.C1C[NH]CCN1
c1ccncc1.C1C[NH]CCN1
HCl
O
140
2
C1CNCCN1.Clc1cnc(Cl)c(Cl)c1>O>Clc1cnc(N2CCNCC2)c(Cl)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-083e1cd12178472ea21d4ea0d900884f
C=C1CC(=O)O1.CC(C)(C)OC(=O)N1CCNCC1>>CC(=O)CC(=O)N1CCN(C(=O)OC(C)(C)C)CC1
C(C)(C)(C)OC(=O)N1CCNCC1.C=C1CC(=O)O1>>C(CC(=O)C)(=O)N1CCN(CC1)C(=O)OC(C)(C)C
[CH2:1]=[C:2]1[O:3][C:5](=[O:6])[CH2:4]1.[NH:7]1[CH2:8][CH2:9][N:10]([C:11](=[O:12])[O:13][C:14]([CH3:15])([CH3:16])[CH3:17])[CH2:18][CH2:19]1>>[CH3:1][C:2](=[O:3])[CH2:4][C:5](=[O:6])[N:7]1[CH2:8][CH2:9][N:10]([C:11](=[O:12])[O:13][C:14]([CH3:15])([CH3:16])[CH3:17])[CH2:18][CH2:19]1
C=C1CC(=O)O1.CC(C)(C)OC(=O)N1CCNCC1
CC(=O)CC(=O)N1CCN(C(=O)OC(C)(C)C)CC1
null
null
CN(C)C=O
Acylation
OtherReaction
4577f8e5153c38d78e55723b317d2862b784dfad0b721d4d59f15977da6300d6
9efa0c835be0aa9453aa895a9d5c6a73c10e08e695158204e8f0348795b4fe67
C1CNCCN1
[#7:1]1-[C:2]-[C:3]-[NH;D2;+0:4]-[C:5]-[C:6]-1.[CH2;D1;+0:7]=[C;H0;D3;+0:8]1-[C:9]-[C;H0;D3;+0:10](=[O;D1;H0:11])-[O;H0;D2;+0:12]-1>>[CH3;D1;+0:7]-[C;H0;D3;+0:8](=[O;H0;D1;+0:12])-[C:9]-[C;H0;D3;+0:10](=[O;D1;H0:11])-[N;H0;D3;+0:4]1-[C:3]-[C:2]-[#7:1]-[C:6]-[C:5]-1
null
[]
null
null
1.5
HOUR
1-tert-Butoxycarbonylpiperazine (5.02 g) was dissolved in DMF (90 mL), and diketene (2.50 mL) was added thereto at room temperature. The mixture was stirred for 1.5 hr and the solvent was evaporated under reduced pressure. Water was added to the residue, and the mixture was extracted with ethyl acetate. The extract was...
10.6084/m9.figshare.5104873.v1
null
Ester.Secondary amine.Vinyl
Ketone.Tertiary amide
C1COC1.C1CNCC[NH]1
C1C[NH]CC[NH]1
C1C[NH]CC[NH]1
null
CN(C)C=O
null
1.5
C=C1CC(=O)O1.CC(C)(C)OC(=O)N1CCNCC1>CN(C)C=O>CC(=O)CC(=O)N1CCN(C(=O)OC(C)(C)C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-fff3605f9f014a9eafe9279be4b48ca9
CC(=O)CC(=O)N1CCN(C(=O)OC(C)(C)C)CC1.CC(C)(C)NN>>Cc1cc(N2CCN(C(=O)OC(C)(C)C)CC2)n(C(C)(C)C)n1
C(CC(=O)C)(=O)N1CCN(CC1)C(=O)OC(C)(C)C.Cl.Cl.Cl.CC1=NN(C(=C1)N1CCN(CC1)[C@H]1C[C@H](NC1)C(=O)N1CSCC1)C1=CC=CC=C1.Cl.C(C)(C)(C)NN>>C(C)(C)(C)OC(=O)N1CCN(CC1)C1=CC(=NN1C(C)(C)C)C
O=[C:2]([CH3:1])[CH2:3][C:4](=O)[N:5]1[CH2:6][CH2:7][N:8]([C:9](=[O:10])[O:11][C:12]([CH3:13])([CH3:14])[CH3:15])[CH2:16][CH2:17]1.[NH:18]([C:19]([CH3:20])([CH3:21])[CH3:22])[NH2:23]>>[CH3:1][c:2]1[cH:3][c:4]([N:5]2[CH2:6][CH2:7][N:8]([C:9](=[O:10])[O:11][C:12]([CH3:13])([CH3:14])[CH3:15])[CH2:16][CH2:17]2)[n:18]([C:19...
CC(=O)CC(=O)N1CCN(C(=O)OC(C)(C)C)CC1.CC(C)(C)NN
Cc1cc(N2CCN(C(=O)OC(C)(C)C)CC2)n(C(C)(C)C)n1
null
null
C(C)O
Aromatic Heterocycle Formation
Pyrazole formation
98c29b40d20c526874877c5fbed4227dd1e6c8e39c4320f02dcfd98c265cd20f
67d101f2f6bbc4d05f99152dec77d6bb3f9da60ddd000ebe4afa876d58cef3b4
c1cc(N2CCNCC2)[nH]n1
O=[C;H0;D3;+0:1](-[C;D1;H3:2])-[CH2;D2;+0:3]-[C;H0;D3;+0:4](=O)-[#7:5](-[C:6])-[C:7].[C;D1;H3:8]-[C:9](-[C;D1;H3:10])(-[C;D1;H3:11])-[NH;D2;+0:12]-[NH2;D1;+0:13]>>[C:6]-[#7:5](-[c;H0;D3;+0:4]1:[cH;D2;+0:3]:[c;H0;D3;+0:1](-[C;D1;H3:2]):[n;H0;D2;+0:13]:[n;H0;D3;+0:12]:1-[C:9](-[C;D1;H3:8])(-[C;D1;H3:10])-[C;D1;H3:11])-[C...
18.9
[{"value": 18.9, "product": "C(C)(C)(C)OC(=O)N1CCN(CC1)C1=CC(=NN1C(C)(C)C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
15
HOUR
1-Acetoacetyl-4-tert-butoxycarbonylpiperazine [product of Example 222 (1), 3.92 g] was dissolved in ethanol (300 mL), and tert-butylhydrazine hydrochloride (1.81 g) and molecular sieves 3A (10 g) were added thereto at room temperature. The mixture was stirred for 15 hr. The reaction mixture was filtrated and the filtra...
10.6084/m9.figshare.5104873.v1
null
Hydrazine.Ketone.Tertiary amide
null
null
c1cc[nH]n1
c1cc[nH]n1.C1C[NH]CC[NH]1
HO-
C(C)O
null
15
CC(=O)CC(=O)N1CCN(C(=O)OC(C)(C)C)CC1.CC(C)(C)NN>C(C)O>Cc1cc(N2CCN(C(=O)OC(C)(C)C)CC2)n(C(C)(C)C)n1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-0ed808e92b9946238c3435597a9880a9
O=C(OCc1ccccc1)N1CCNCC1.S=C=Nc1ccccc1>>O=C(OCc1ccccc1)N1CCN(C(=S)Nc2ccccc2)CC1
C(C1=CC=CC=C1)OC(=O)N1CCNCC1.C1(=CC=CC=C1)N=C=S>>N(C1=CC=CC=C1)C(=S)N1CCN(CC1)C(=O)OCC1=CC=CC=C1
[O:1]=[C:2]([O:3][CH2:4][c:5]1[cH:6][cH:7][cH:8][cH:9][cH:10]1)[N:11]1[CH2:12][CH2:13][NH:14][CH2:24][CH2:25]1.[C:15](=[S:16])=[N:17][c:18]1[cH:19][cH:20][cH:21][cH:22][cH:23]1>>[O:1]=[C:2]([O:3][CH2:4][c:5]1[cH:6][cH:7][cH:8][cH:9][cH:10]1)[N:11]1[CH2:12][CH2:13][N:14]([C:15](=[S:16])[NH:17][c:18]2[cH:19][cH:20][cH:21...
O=C(OCc1ccccc1)N1CCNCC1.S=C=Nc1ccccc1
O=C(OCc1ccccc1)N1CCN(C(=S)Nc2ccccc2)CC1
null
null
CC(=O)C
Heteroatom Alkylation and Arylation
thiourea
beb066691ff40a37c26bc4234840e891c6843c6d14f49542e84576855b81b429
48e0e6261e922bdea79c78ea511461d733cbd49c10100c782d86c83675c4be7c
O=C(OCc1ccccc1)N1CCN(C(=S)Nc2ccccc2)CC1
[#7:1]1-[C:2]-[C:3]-[NH;D2;+0:4]-[C:5]-[C:6]-1.[S;D1;H0:7]=[C;H0;D2;+0:8]=[N;H0;D2;+0:9]-[c:10](:[c:11]):[c:12]>>[S;D1;H0:7]=[C;H0;D3;+0:8](-[NH;D2;+0:9]-[c:10](:[c:11]):[c:12])-[N;H0;D3;+0:4]1-[C:3]-[C:2]-[#7:1]-[C:6]-[C:5]-1
null
[]
null
null
1
HOUR
1-Benzyloxycarbonylpiperazine (5.00 g) was dissolved in acetone (50 mL), and phenyl isothiocyanate (2.9 mL) was added thereto under ice-cooling. The mixture was stirred at room temperature for 1 hr. The precipitated solid was collected by filtration to give 1-(anilinocarbothioyl)-4-(benzyloxycarbonyl)piperazine (5.08 g...
10.6084/m9.figshare.5104873.v1
null
Secondary amine.Isothiocyanate
Thiourea
C1C[NH]CCN1
C1C[NH]CC[NH]1
c1ccccc1.C1C[NH]CC[NH]1.c1ccccc1
null
CC(=O)C
null
1
O=C(OCc1ccccc1)N1CCNCC1.S=C=Nc1ccccc1>CC(=O)C>O=C(OCc1ccccc1)N1CCN(C(=S)Nc2ccccc2)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-042cd53d25eb4022aafcc06889b6859c
C#CCN.CSC(=Nc1ccccc1)N1CCN(C(=O)OCc2ccccc2)CC1>>Cc1cnc(N2CCN(C(=O)OCc3ccccc3)CC2)n1-c1ccccc1
O.C1(=CC=C(C=C1)S(=O)(=O)O)C.C(C1=CC=CC=C1)OC(=O)N1CCN(CC1)C(=NC1=CC=CC=C1)SC.Cl.Cl.Cl.C1(=CC=CC=C1)N1C(=NC=C1)N1CCN(CC1)[C@H]1C[C@H](NC1)C(=O)N1CSCC1.C(C#C)N>>C(C1=CC=CC=C1)OC(=O)N1CCN(CC1)C=1N(C(=CN1)C)C1=CC=CC=C1
[CH:1]#[C:2][CH2:3][NH2:4].CS[C:5]([N:6]1[CH2:7][CH2:8][N:9]([C:10](=[O:11])[O:12][CH2:13][c:14]2[cH:15][cH:16][cH:17][cH:18][cH:19]2)[CH2:20][CH2:21]1)=[N:22][c:23]1[cH:24][cH:25][cH:26][cH:27][cH:28]1>>[CH3:1][c:2]1[cH:3][n:4][c:5]([N:6]2[CH2:7][CH2:8][N:9]([C:10](=[O:11])[O:12][CH2:13][c:14]3[cH:15][cH:16][cH:17][cH...
C#CCN.CSC(=Nc1ccccc1)N1CCN(C(=O)OCc2ccccc2)CC1
Cc1cnc(N2CCN(C(=O)OCc3ccccc3)CC2)n1-c1ccccc1
null
null
C(CCC)O
Aromatic Heterocycle Formation
OtherReaction
73ac30e747e4229428260662dbb12dd45b5d2176b6d4b63c7267db806047c81f
4c8e418b01f6182030f1526ea2fcf5c0ebd529284eb47d16a13d089a87d05fd0
O=C(OCc1ccccc1)N1CCN(c2nccn2-c2ccccc2)CC1
C-S-[C;H0;D3;+0:1](=[N;H0;D2;+0:2]-[c;H0;D3;+0:3](:[c:4]:[c:5]):[c:6]:[c:7])-[#7:8](-[C:9])-[C:10].[CH;D1;+0:11]#[C;H0;D2;+0:12]-[CH2;D2;+0:13]-[NH2;D1;+0:14]>>[C:9]-[#7:8](-[c;H0;D3;+0:1]1:[n;H0;D2;+0:14]:[cH;D2;+0:13]:[c;H0;D3;+0:12](-[CH3;D1;+0:11]):[n;H0;D3;+0:2]:1-[c;H0;D3;+0:3](:[c:4]:[c:5]):[c:6]:[c:7])-[C:10]
null
[]
null
null
null
null
1-Benzyloxycarbonyl-4-[(methylthio)phenyliminomethyl]piperazine [product of Example 224 (2), 2.70 g] and propargylamine (2.3 mL) were dissolved in 1-butanol (25 mL), and p-toluenesulfonic acid monohydrate (156 mg) was added thereto. The mixture was refluxed for 20 hr. The reaction mixture was concentrated under reduced...
10.6084/m9.figshare.5104873.v1
null
Primary amine.Monosulfide.Alkyne
null
null
c1c[nH]cn1
c1c[nH]cn1.C1C[NH]CC[NH]1.c1ccccc1.c1ccccc1
Other
C(CCC)O
null
null
C#CCN.CSC(=Nc1ccccc1)N1CCN(C(=O)OCc2ccccc2)CC1>C(CCC)O>Cc1cnc(N2CCN(C(=O)OCc3ccccc3)CC2)n1-c1ccccc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-a138f0e4d992421a948682e1f55043e6
C1CNCCN1.Clc1nnnn1-c1ccccc1>>c1ccc(-n2nnnc2N2CCNCC2)cc1
ClC1=NN=NN1C1=CC=CC=C1.N1CCNCC1>>C1(=CC=CC=C1)N1N=NN=C1N1CCNCC1
[NH:10]1[CH2:11][CH2:12][NH:13][CH2:14][CH2:15]1.Cl[c:9]1[n:5](-[c:4]2[cH:3][cH:2][cH:1][cH:17][cH:16]2)[n:6][n:7][n:8]1>>[cH:1]1[cH:2][cH:3][c:4](-[n:5]2[n:6][n:7][n:8][c:9]2[N:10]2[CH2:11][CH2:12][NH:13][CH2:14][CH2:15]2)[cH:16][cH:17]1
C1CNCCN1.Clc1nnnn1-c1ccccc1
c1ccc(-n2nnnc2N2CCNCC2)cc1
null
null
null
Heteroatom Alkylation and Arylation
Ullmann-Goldberg Substitution amine
4370c4208f04c18549baf32cb111eed2207b9d9119be11b2c908568f35fda136
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
c1ccc(-n2nnnc2N2CCNCC2)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[#7;a:3]:[#7;a:4]:[#7;a:5]:1-[c:6].[#7:7]1-[C:8]-[C:9]-[NH;D2;+0:10]-[C:11]-[C:12]-1>>[c:6]-[#7;a:5]1:[#7;a:4]:[#7;a:3]:[#7;a:2]:[c;H0;D3;+0:1]:1-[N;H0;D3;+0:10]1-[C:9]-[C:8]-[#7:7]-[C:12]-[C:11]-1
99.7
[{"value": 99.7, "product": "C1(=CC=CC=C1)N1N=NN=C1N1CCNCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using 5-chloro-1-phenyl-1H-tetrazol (2.10 g) and piperazine (10.0 g), and reaction at 100° C. in the same manner as in Example 196 (1), 1-(1-phenyl-1H-tetrazol-5-yl)piperazine (2.67 g) was obtained as a pale-yellow powder. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CNCCN1.c1nnn[nH]1
c1nnn[nH]1.C1C[NH]CCN1
c1ccccc1.c1nnn[nH]1.C1C[NH]CCN1
HCl
null
null
null
C1CNCCN1.Clc1nnnn1-c1ccccc1>>c1ccc(-n2nnnc2N2CCNCC2)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-8e62a5004f074b199fdeda059775825a
N#Cc1ccc(N)c([N+](=O)[O-])c1>>N#Cc1ccc(N)c(N)c1
NC1=C(C=C(C#N)C=C1)[N+](=O)[O-]>>NC=1C=C(C#N)C=CC1N
O=[N+:9]([O-])[c:8]1[c:6]([NH2:7])[cH:5][cH:4][c:3]([C:2]#[N:1])[cH:10]1>>[N:1]#[C:2][c:3]1[cH:4][cH:5][c:6]([NH2:7])[c:8]([NH2:9])[cH:10]1
N#Cc1ccc(N)c([N+](=O)[O-])c1
N#Cc1ccc(N)c(N)c1
null
[Pd]
O1CCCC1.CO
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
c1ccccc1
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
98
[{"value": 98.0, "product": "NC=1C=C(C#N)C=CC1N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
4-Amino-3-nitrobenzonitrile (25 g) was dissolved in methanol (200 mL) and tetrahydrofuran (200 mL). The mixture was stirred in the presence of 10% palladium/carbon (3.0 g) under a hydrogen atomosphere (1 atm) for 20 hr. The reaction mixture was filtrated and the filtrate was concentrated under reduced pressure to give ...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1ccccc1
Other
[Pd].O1CCCC1.CO
null
null
N#Cc1ccc(N)c([N+](=O)[O-])c1>[Pd].O1CCCC1.CO>N#Cc1ccc(N)c(N)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-26147d012fea46848867a779534fd71d
Clc1nc2ccccc2[nH]1.O=C1CCC(=O)N1Cl>>Clc1ccc2nc(Cl)[nH]c2c1
ClC=1NC2=C(N1)C=CC=C2.ClN1C(CCC1=O)=O.O>>ClC=1NC2=C(N1)C=CC(=C2)Cl
[cH:2]1[cH:3][cH:4][c:5]2[n:6][c:7]([Cl:8])[nH:9][c:10]2[cH:11]1.O=C1CCC(=O)N1[Cl:1]>>[Cl:1][c:2]1[cH:3][cH:4][c:5]2[n:6][c:7]([Cl:8])[nH:9][c:10]2[cH:11]1
Clc1nc2ccccc2[nH]1.O=C1CCC(=O)N1Cl
Clc1ccc2nc(Cl)[nH]c2c1
null
null
CN(C)C=O
Functional Group Interconversion
Chlorination
fbcb510fe012bb024cb5d3ac9e0bf4b976f46e215ed905e0c24c89cd8edf8077
0e444576b73669992a4073cc3f7b10ed52cb9df09f9f8e4042e39e6a602aa390
c1ccc2[nH]cnc2c1
O=C1-C-C-C(=O)-N-1-[Cl;H0;D1;+0:1].[#7;a:2]1:[c:3]:[#7;a:4]:[c:5]2:[c:6]:[cH;D2;+0:7]:[c:8]:[c:9]:[c:10]:1:2>>[Cl;H0;D1;+0:1]-[c;H0;D3;+0:7]1:[c:6]:[c:5]2:[#7;a:4]:[c:3]:[#7;a:2]:[c:10]:2:[c:9]:[c:8]:1
37.3
[{"value": 37.3, "product": "ClC=1NC2=C(N1)C=CC(=C2)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
60
CELSIUS
30
MINUTE
2-Chlorobenzimidazole (1.05 g) was dissolved in DMF (10 mL), and N-chlorosuccinimide (1.01 g) was added thereto. The mixture was stirred at 60° C. for 30 min and the reaction mixture was added to water. The precipitated solid was collected by filtration to give 2,5-dichlorobenzimidazole (0.480 g) as a white solid. Cond...
10.6084/m9.figshare.5104873.v1
null
Tertiary amide.Tertiary amide
Aromatic halide
c1ccc2[nH]cnc2c1.C1CCNC1
c1ccc2[nH]cnc2c1
c1ccc2[nH]cnc2c1
HO-
CN(C)C=O
60
0.5
Clc1nc2ccccc2[nH]1.O=C1CCC(=O)N1Cl>CN(C)C=O>Clc1ccc2nc(Cl)[nH]c2c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-5e9ba6ad0e98430d9baae746e4614fd4
CI.Clc1nc2ccccc2[nH]1>>Cn1c(Cl)nc2ccccc21
O.[H-].[Na+].ClC=1NC2=C(N1)C=CC=C2.CI>>ClC1=NC2=C(N1C)C=CC=C2
I[CH3:1].[nH:2]1[c:3]([Cl:4])[n:5][c:6]2[cH:7][cH:8][cH:9][cH:10][c:11]12>>[CH3:1][n:2]1[c:3]([Cl:4])[n:5][c:6]2[cH:7][cH:8][cH:9][cH:10][c:11]12
CI.Clc1nc2ccccc2[nH]1
Cn1c(Cl)nc2ccccc21
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
b959860a194ba554eb04b7d214c30055f34ef752b392c88b943b67fec007e3e6
7a358c636daddc97c1fb4c29f378044d7eac3f01815d9966e599841f642d631a
c1ccc2[nH]cnc2c1
I-[CH3;D1;+0:1].[Cl;D1;H0:2]-[c:3]1:[#7;a:4]:[c:5](:[c:6]):[c:7](:[c:8]):[nH;D2;+0:9]:1>>[CH3;D1;+0:1]-[n;H0;D3;+0:9]1:[c:7](:[c:8]):[c:5](:[c:6]):[#7;a:4]:[c:3]:1-[Cl;D1;H0:2]
null
[]
null
null
30
MINUTE
Sodium hydride (contained by 60%, 0.288 g) was suspended in DMF (10 mL), and 2-chlorobenzimidazole (1 g) was added thereto. The mixture was stirred at room temperature for 30 min and methyl iodide (0.61 mL) was added thereto. After stirring at room temperature for 1 hr, water was added to the reaction mixture. The mixt...
10.6084/m9.figshare.5104873.v1
null
null
null
c1ccc2[nH]cnc2c1
c1nc2ccccc2[nH]1
c1nc2ccccc2[nH]1
HI
CN(C)C=O
null
0.5
CI.Clc1nc2ccccc2[nH]1>CN(C)C=O>Cn1c(Cl)nc2ccccc21
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-e3a335ea328f4a87b63664f41e90b9a5
CN.O=[N+]([O-])c1cc(C(F)(F)F)ccc1F>>CNc1ccc(C(F)(F)F)cc1[N+](=O)[O-]
FC1=C(C=C(C=C1)C(F)(F)F)[N+](=O)[O-].CN.C(C)O.O>>CNC1=C(C=C(C=C1)C(F)(F)F)[N+](=O)[O-]
[CH3:1][NH2:2].F[c:3]1[cH:4][cH:5][c:6]([C:7]([F:8])([F:9])[F:10])[cH:11][c:12]1[N+:13](=[O:14])[O-:15]>>[CH3:1][NH:2][c:3]1[cH:4][cH:5][c:6]([C:7]([F:8])([F:9])[F:10])[cH:11][c:12]1[N+:13](=[O:14])[O-:15]
CN.O=[N+]([O-])c1cc(C(F)(F)F)ccc1F
CNc1ccc(C(F)(F)F)cc1[N+](=O)[O-]
null
null
C(C)O
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation primary amine
da9dae6a655c4bd18887b692f91621e77027436294d6e1fc7be7295afb364796
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccccc1
F-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[#7;+:5]):[c:6].[C;D1;H3:7]-[NH2;D1;+0:8]>>[#7;+:5]-[c:4](:[c:6]):[c;H0;D3;+0:1](-[NH;D2;+0:8]-[C;D1;H3:7]):[c:2]:[c:3]
96.9
[{"value": 96.9, "product": "CNC1=C(C=C(C=C1)C(F)(F)F)[N+](=O)[O-]", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
40
MINUTE
4-Fluoro-3-nitrobenzotrifluoride (25 g) was dissolved in ethanol (50 mL), and 30% methylamine-ethanol solution (97.9 g) was gradually added dropwise under ice-cooling, and the mixture was stirred at room temperature for 40 min. The reaction mixture was added to water, and the precipitated solid was collected by filtrat...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccccc1
c1ccccc1
c1ccccc1
HF
C(C)O
null
0.666667
CN.O=[N+]([O-])c1cc(C(F)(F)F)ccc1F>C(C)O>CNc1ccc(C(F)(F)F)cc1[N+](=O)[O-]
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-ca9eb8ff3b4e49cd9faf6813ffe9e145
CCOC(=S)[S-].Nc1cc([N+](=O)[O-])ccc1Br>>O=[N+]([O-])c1ccc2sc(S)nc2c1
BrC1=C(N)C=C(C=C1)[N+](=O)[O-].C(C)OC(=S)[S-].[K+]>>SC=1SC2=C(N1)C=C(C=C2)[N+](=O)[O-]
CCO[C:9]([S-:8])=[S:10].Br[c:7]1[cH:6][cH:5][c:4]([N+:2](=[O:1])[O-:3])[cH:13][c:12]1[NH2:11]>>[O:1]=[N+:2]([O-:3])[c:4]1[cH:5][cH:6][c:7]2[s:8][c:9]([SH:10])[n:11][c:12]2[cH:13]1
CCOC(=S)[S-].Nc1cc([N+](=O)[O-])ccc1Br
O=[N+]([O-])c1ccc2sc(S)nc2c1
null
null
CN1C(CCC1)=O
Aromatic Heterocycle Formation
OtherReaction
02db7beb47c6da870010e245f6db10a58d2bc4b2e2c685b01f3605f7a3cf723b
f9c9e1616cbfafcf863bdd1e9fe84bb954b8f3b409b7bf896e5abd1affbe360c
c1ccc2scnc2c1
Br-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[NH2;D1;+0:5]):[c:6].C-C-O-[C;H0;D3;+0:7](-[S-;H0;D1:8])=[S;H0;D1;+0:9]>>[SH;D1;+0:9]-[c;H0;D3;+0:7]1:[n;H0;D2;+0:5]:[c:4](:[c:6]):[c;H0;D3;+0:1](:[c:2]:[c:3]):[s;H0;D2;+0:8]:1
86.2
[{"value": 86.2, "product": "SC=1SC2=C(N1)C=C(C=C2)[N+](=O)[O-]", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
140
CELSIUS
null
null
2-Bromo-5-nitroaniline (10 g) was dissolved in N-methyl-2-pyrrolidone (50 mL), and potassium ethylxanthate (14.8 g) was added thereto. The mixture was stirred at 140° C. with heating. The reaction mixture was concentrated under reduced pressure, and water (300 mL) and conc. hydrochloric acid (10 mL) were added to the r...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Ether.Primary amine.Thiocarbonyl
Aromatic thiol
c1ccccc1
c1ccc2scnc2c1
c1ccc2scnc2c1
HBr
CN1C(CCC1)=O
140
null
CCOC(=S)[S-].Nc1cc([N+](=O)[O-])ccc1Br>CN1C(CCC1)=O>O=[N+]([O-])c1ccc2sc(S)nc2c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-4de3f2addb3c4a68bcd3fc84a411955c
CN(C)C=O.O=[N+]([O-])c1ccc2nc(S)sc2c1>>CSc1nc2ccc([N+](=O)[O-])cc2s1
[H-].[Na+].SC=1SC2=C(N1)C=CC(=C2)[N+](=O)[O-].CN(C)C=O>>CSC=1SC2=C(N1)C=CC(=C2)[N+](=O)[O-]
CN(C=O)[CH3:1].[SH:2][c:3]1[n:4][c:5]2[cH:6][cH:7][c:8]([N+:9](=[O:10])[O-:11])[cH:12][c:13]2[s:14]1>>[CH3:1][S:2][c:3]1[n:4][c:5]2[cH:6][cH:7][c:8]([N+:9](=[O:10])[O-:11])[cH:12][c:13]2[s:14]1
CN(C)C=O.O=[N+]([O-])c1ccc2nc(S)sc2c1
CSc1nc2ccc([N+](=O)[O-])cc2s1
null
null
null
Heteroatom Alkylation and Arylation
S-methylation
931eb9954dd138479cd7340b2b0ff5ba38d3e11935f9dd9ea63aa3dfd63853ff
52869605e231957850ab88e7d5013b32cc121894e7d0d1cc33e1915e04b9e0b9
c1ccc2scnc2c1
C-N(-[CH3;D1;+0:1])-C=O.[SH;D1;+0:2]-[c:3]1:[#16;a:4]:[c:5]:[c:6]:[#7;a:7]:1>>[CH3;D1;+0:1]-[S;H0;D2;+0:2]-[c:3]1:[#16;a:4]:[c:5]:[c:6]:[#7;a:7]:1
null
[]
null
null
18
HOUR
Sodium hydride (containing by 60%, 6.15 g) was suspended in DMF (120 mL) and 2-mercapto-6-nitrobenzothiazole (20 g) was added thereto under ice-cooling. After completion of bubbling, methyl iodide (26.4 mL) was added thereto. The mixture was stirred at room temperature for 18 hr. Water (800 mL) was added to the reactio...
10.6084/m9.figshare.5104873.v1
null
Tertiary amide.Aromatic thiol
Monosulfide
null
null
c1ccc2scnc2c1
HO-
null
null
18
CN(C)C=O.O=[N+]([O-])c1ccc2nc(S)sc2c1>>CSc1nc2ccc([N+](=O)[O-])cc2s1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-75d7e96e81334e7c8e9c2b8f6a7049a2
CCOC(=S)[S-].Nc1ccc(C(F)(F)F)cc1Br>>FC(F)(F)c1ccc2nc(S)sc2c1
NC1=C(C=C(C=C1)C(F)(F)F)Br.C(C)OC(=S)[S-].[K+].O>>FC(C1=CC2=C(N=C(S2)S)C=C1)(F)F
CCO[C:10](=[S:11])[S-:12].Br[c:13]1[c:8]([NH2:9])[cH:7][cH:6][c:5]([C:2]([F:1])([F:3])[F:4])[cH:14]1>>[F:1][C:2]([F:3])([F:4])[c:5]1[cH:6][cH:7][c:8]2[n:9][c:10]([SH:11])[s:12][c:13]2[cH:14]1
CCOC(=S)[S-].Nc1ccc(C(F)(F)F)cc1Br
FC(F)(F)c1ccc2nc(S)sc2c1
null
null
CN1C(CCC1)=O
Aromatic Heterocycle Formation
OtherReaction
02db7beb47c6da870010e245f6db10a58d2bc4b2e2c685b01f3605f7a3cf723b
f9c9e1616cbfafcf863bdd1e9fe84bb954b8f3b409b7bf896e5abd1affbe360c
c1ccc2scnc2c1
Br-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[NH2;D1;+0:5]):[c:6].C-C-O-[C;H0;D3;+0:7](-[S-;H0;D1:8])=[S;H0;D1;+0:9]>>[SH;D1;+0:9]-[c;H0;D3;+0:7]1:[n;H0;D2;+0:5]:[c:4](:[c:6]):[c;H0;D3;+0:1](:[c:2]:[c:3]):[s;H0;D2;+0:8]:1
25.8
[{"value": 25.8, "product": "FC(C1=CC2=C(N=C(S2)S)C=C1)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
160
CELSIUS
3
HOUR
4-Amino-3-bromobenzotrifluoride (2.40 g) was dissolved in N-methyl-2-pyrrolidone (10 mL), and potassium ethylxanthate (3.52 g) was added thereto. The mixture was stirred at 160° C. for 3 hr with heating. Water (300 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Ether.Primary amine.Thiocarbonyl
Aromatic thiol
c1ccccc1
c1ccc2scnc2c1
c1ccc2scnc2c1
HBr
CN1C(CCC1)=O
160
3
CCOC(=S)[S-].Nc1ccc(C(F)(F)F)cc1Br>CN1C(CCC1)=O>FC(F)(F)c1ccc2nc(S)sc2c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-44cd83b575bd42f9936fd736835dfe85
BrBr.CC(C)Oc1ccc(N)cc1>>CC(C)Oc1ccc(N)c(Br)c1
C(C)(C)OC1=CC=C(N)C=C1.BrBr>>BrC1=C(N)C=CC(=C1)OC(C)C
Br[Br:11].[CH3:1][CH:2]([CH3:3])[O:4][c:5]1[cH:6][cH:7][c:8]([NH2:9])[cH:10][cH:12]1>>[CH3:1][CH:2]([CH3:3])[O:4][c:5]1[cH:6][cH:7][c:8]([NH2:9])[c:10]([Br:11])[cH:12]1
BrBr.CC(C)Oc1ccc(N)cc1
CC(C)Oc1ccc(N)c(Br)c1
null
null
C(C)(=O)O
Functional Group Interconversion
Bromination
f6effe61353895b318215d8bd9b6bb1105cafbf7be8c217d748df587260b32c3
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
c1ccccc1
Br-[Br;H0;D1;+0:1].[N;D1;H2:2]-[c:3](:[c:4]):[cH;D2;+0:5]:[c:6]:[c:7]>>[Br;H0;D1;+0:1]-[c;H0;D3;+0:5](:[c:6]:[c:7]):[c:3](-[N;D1;H2:2]):[c:4]
null
[]
null
null
2
HOUR
4-Isopropoxyaniline (24.2 g) was dissolved in acetic acid (300 mL), and a mixture of bromine (8.25 mL) and acetic acid (80 mL) was added dropwise. After stirring at room temperature for 2 hr, the reaction mixture was concentrated under reduced pressure. Water was added to residue, and the mixture was extracted with die...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ccccc1
c1ccccc1
c1ccccc1
HBr
C(C)(=O)O
null
2
BrBr.CC(C)Oc1ccc(N)cc1>C(C)(=O)O>CC(C)Oc1ccc(N)c(Br)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-219e30c1dca24637845e5b3d4c9459db
Clc1nc2ccccc2s1.O=[N+]([O-])O>>O=[N+]([O-])c1ccc2nc(Cl)sc2c1
S(O)(O)(=O)=O.ClC=1SC2=C(N1)C=CC=C2.[N+](=O)(O)[O-]>>ClC=1SC2=C(N1)C=CC(=C2)[N+](=O)[O-]
[cH:4]1[cH:5][cH:6][c:7]2[n:8][c:9]([Cl:10])[s:11][c:12]2[cH:13]1.O[N+:2](=[O:1])[O-:3]>>[O:1]=[N+:2]([O-:3])[c:4]1[cH:5][cH:6][c:7]2[n:8][c:9]([Cl:10])[s:11][c:12]2[cH:13]1
Clc1nc2ccccc2s1.O=[N+]([O-])O
O=[N+]([O-])c1ccc2nc(Cl)sc2c1
null
null
O
Functional Group Addition
Aromatic nitration with HNO3
668b9c8f526506609a3c1bae67dc3186759376057ca0511251a32d7865e504f8
ddce49825c02b8965f10c8d99e3c841d26e1f136da6037b417c09313e6d73097
c1ccc2scnc2c1
O-[N+;H0;D3:1](-[O;-;D1;H0:2])=[O;D1;H0:3].[#16;a:4]1:[c:5]:[#7;a:6]:[c:7]2:[c:8]:[c:9]:[cH;D2;+0:10]:[c:11]:[c:12]:1:2>>[O;-;D1;H0:2]-[N+;H0;D3:1](=[O;D1;H0:3])-[c;H0;D3;+0:10]1:[c:11]:[c:12]2:[#16;a:4]:[c:5]:[#7;a:6]:[c:7]:2:[c:8]:[c:9]:1
null
[]
null
null
null
null
Conc. sulfuric acid (50 mL) was added to 2-chlorobenzothiazole (10 g) under ice-cooling, and conc. nitric acid (5 mL) was added dropwise under ice-cooling. The mixture was stirred under ice-cooling for 1 hr, and iced water (600 mL) was added to the reaction mixture. The precipitated solid was collected by filtration, w...
10.6084/m9.figshare.5104873.v1
null
Nitrate
Nitro group
c1ccc2scnc2c1
c1ccc2scnc2c1
c1ccc2scnc2c1
HO-
O
null
null
Clc1nc2ccccc2s1.O=[N+]([O-])O>O>O=[N+]([O-])c1ccc2nc(Cl)sc2c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-4f3cc27de9b54598aeb7b5073ac9d63b
CCOC(=O)c1ccccc1O.[NH3+]O>>O=C(NO)c1ccccc1O
Cl.O[NH3+].C(C=1C(O)=CC=CC1)(=O)OCC>>C(C=1C(O)=CC=CC1)(=O)NO
CCO[C:2](=[O:1])[c:5]1[cH:6][cH:7][cH:8][cH:9][c:10]1[OH:11].[NH3+:3][OH:4]>>[O:1]=[C:2]([NH:3][OH:4])[c:5]1[cH:6][cH:7][cH:8][cH:9][c:10]1[OH:11]
CCOC(=O)c1ccccc1O.[NH3+]O
O=C(NO)c1ccccc1O
null
null
O1CCOCC1.[OH-].[Na+]
Acylation
OtherReaction
2d87d4ce8b797d207a4d720ddca5314a71ae21452d103320c99ec97070478dba
00b364fcf2d2396af24ca4500c386e4a8a422045f0a912c21eff7cf619606bb9
c1ccccc1
C-C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[NH3+;D1:6]-[O;D1;H1:7]>>[O;D1;H0:2]=[C;H0;D3;+0:1](-[NH;D2;+0:6]-[O;D1;H1:7])-[c:3](:[c:4]):[c:5]
54.3
[{"value": 54.3, "product": "C(C=1C(O)=CC=CC1)(=O)NO", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
5
HOUR
Hydroxylammonium hydrochloride (15 g) was dissolved in 10% aqueous sodium hydroxide solution (220 mL), and a solution of ethyl salicylate (24 g) in 1,4-dioxane (70 mL) was gradually added, and the mixture was stirred at room temperature for 5 hr. The reaction mixture was concentrated until the amount thereof became alm...
10.6084/m9.figshare.5104873.v1
null
Ester
Secondary amide
null
null
c1ccccc1
HO-
O1CCOCC1.[OH-].[Na+]
null
5
CCOC(=O)c1ccccc1O.[NH3+]O>O1CCOCC1.[OH-].[Na+]>O=C(NO)c1ccccc1O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-2ef8d76b7e7c40c7ab4635c843fc3db3
BrBr.COC(=O)c1ccccc1O>>COC(=O)c1cc(Br)ccc1O
C(C=1C(O)=CC=CC1)(=O)OC.BrBr.O>>BrC1=CC=C(C(C(=O)OC)=C1)O
Br[Br:8].[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][cH:9][cH:10][c:11]1[OH:12]>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][c:7]([Br:8])[cH:9][cH:10][c:11]1[OH:12]
BrBr.COC(=O)c1ccccc1O
COC(=O)c1cc(Br)ccc1O
null
null
C(C)(=O)O
Functional Group Interconversion
Bromination
f6effe61353895b318215d8bd9b6bb1105cafbf7be8c217d748df587260b32c3
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
c1ccccc1
Br-[Br;H0;D1;+0:1].[#8:2]-[C:3](=[O;D1;H0:4])-[c:5]:[c:6]:[cH;D2;+0:7]:[c:8]:[c:9]>>[#8:2]-[C:3](=[O;D1;H0:4])-[c:5]:[c:6]:[c;H0;D3;+0:7](-[Br;H0;D1;+0:1]):[c:8]:[c:9]
null
[]
null
null
21
HOUR
Methyl salicylate (149 g) was dissolved in acetic acid (900 mL), and bromine (50 mL) was added thereto. The mixture was stirred at room temperature for 21 hr. Water (10 L) was added to the reaction mixture, and the precipitated solid was collected by filtration, which was then recrystallized from methanol to give methy...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ccccc1
c1ccccc1
c1ccccc1
HBr
C(C)(=O)O
null
21
BrBr.COC(=O)c1ccccc1O>C(C)(=O)O>COC(=O)c1cc(Br)ccc1O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-60dd5431afaf477babfb87ec33d04de8
Nc1ncccc1O>>Sc1nc2ncccc2o1
C(C)OC(=S)[S-].[K+].NC1=NC=CC=C1O.O.Cl>>O1C(=NC2=NC=CC=C21)S
[NH2:3][c:4]1[n:5][cH:6][cH:7][cH:8][c:9]1[OH:10]>>[SH:1][c:2]1[n:3][c:4]2[n:5][cH:6][cH:7][cH:8][c:9]2[o:10]1
Nc1ncccc1O
Sc1nc2ncccc2o1
null
null
N1=CC=CC=C1
Aromatic Heterocycle Formation
OtherReaction
41e8a4c852be5f8941b1a63345cbe497a313afe0c537ae18d00f7d68d3792051
43a68e502bebb4894b205d94c44e8d052be6ce3d241cfadf7f1d04b13c7f9ab7
c1cnc2ncoc2c1
[NH2;D1;+0:1]-[c:2](:[#7;a:3]:[c:4]):[c:5](-[OH;D1;+0:6]):[c:7]>>[S;D1;H1:8]-[c:9]1:[n;H0;D2;+0:1]:[c:2](:[#7;a:3]:[c:4]):[c:5](:[c:7]):[o;H0;D2;+0:6]:1
67.4
[{"value": 67.4, "product": "O1C(=NC2=NC=CC=C21)S", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
2-Amino-3-hydroxypyridine (5.51 g) was dissolved in pyridine (100 mL), and potassium ethylxanthate (8.82 g) was added thereto. The mixture was refluxed for 2 hr. Iced water (400 mL) was added to the reaction mixture, and concentrated hydrochloric acid (40 mL) was added thereto. The mixture was extracted with chloroform...
10.6084/m9.figshare.5104873.v1
null
Aromatic alcohol.Primary amine
Aromatic thiol
c1ccncc1
c1cnc2ncoc2c1
c1cnc2ncoc2c1
Other
N1=CC=CC=C1
null
null
Nc1ncccc1O>N1=CC=CC=C1>Sc1nc2ncccc2o1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-d4b4c6110f8743b0a1fd6fdb3c424c09
C1CNCCN1.CCOC(=O)C(C)(C)c1cn2nc(Cl)ccc2n1>>CCOC(=O)C(C)(C)c1cn2nc(N3CCNCC3)ccc2n1
ClC=1C=CC=2N(N1)C=C(N2)C(C(=O)OCC)(C)C.N1CCNCC1>>C(C)OC(=O)C(C)(C)C=1N=C2N(N=C(C=C2)N2CCNCC2)C1
[NH:14]1[CH2:15][CH2:16][NH:17][CH2:18][CH2:19]1.Cl[c:13]1[n:12][n:11]2[cH:10][c:9]([C:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])([CH3:7])[CH3:8])[n:23][c:22]2[cH:21][cH:20]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[C:6]([CH3:7])([CH3:8])[c:9]1[cH:10][n:11]2[n:12][c:13]([N:14]3[CH2:15][CH2:16][NH:17][CH2:18][CH2:19]3)[cH:20][cH:21]...
C1CNCCN1.CCOC(=O)C(C)(C)c1cn2nc(Cl)ccc2n1
CCOC(=O)C(C)(C)c1cn2nc(N3CCNCC3)ccc2n1
null
null
null
Heteroatom Alkylation and Arylation
Ullmann-Goldberg Substitution amine
6f8fbd59e8065cb5d16a4ee70ca3b28d0ef327664784d16ab1e6dc53fb9f46d3
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
c1cn2nc(N3CCNCC3)ccc2n1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[#7;a:3]2:[c:4]:[c:5]:[#7;a:6]:[c:7]:2:[c:8]:[c:9]:1.[#7:10]1-[C:11]-[C:12]-[NH;D2;+0:13]-[C:14]-[C:15]-1>>[#7:10]1-[C:11]-[C:12]-[N;H0;D3;+0:13](-[c;H0;D3;+0:1]2:[#7;a:2]:[#7;a:3]3:[c:4]:[c:5]:[#7;a:6]:[c:7]:3:[c:8]:[c:9]:2)-[C:14]-[C:15]-1
100
[{"value": 100.0, "product": "C(C)OC(=O)C(C)(C)C=1N=C2N(N=C(C=C2)N2CCNCC2)C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using ethyl 2-(6-chloroimidazo[1,2-b]pyridazin-2-yl)-2-methylpropionate (2.00 g) and piperazine (19.7 g), and by a reaction at 100° C. in the same manner as in Example 196 (1), 1-[2-(1-ethoxycarbonyl-1-methylethyl)-6-imidazo[1,2-b]pyridazinyl]piperazine (2.37 g) was obtained as an oil. Conditions: See reaction.notes.pr...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CNCCN1.c1cnn2ccnc2c1
c1cnn2ccnc2c1.C1C[NH]CCN1
c1cnn2ccnc2c1.C1C[NH]CCN1
HCl
null
null
null
C1CNCCN1.CCOC(=O)C(C)(C)c1cn2nc(Cl)ccc2n1>>CCOC(=O)C(C)(C)c1cn2nc(N3CCNCC3)ccc2n1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-3e2bf5b0eeed4dbba026aa20889124f7
Cc1cc(O)c2ccccc2n1.O=P(Cl)(Cl)Cl>>Cc1cc(Cl)c2ccccc2n1
OC1=CC(=NC2=CC=CC=C12)C.P(=O)(Cl)(Cl)Cl>>ClC1=CC(=NC2=CC=CC=C12)C
O[c:4]1[cH:3][c:2]([CH3:1])[n:12][c:11]2[c:6]1[cH:7][cH:8][cH:9][cH:10]2.O=P(Cl)(Cl)[Cl:5]>>[CH3:1][c:2]1[cH:3][c:4]([Cl:5])[c:6]2[cH:7][cH:8][cH:9][cH:10][c:11]2[n:12]1
Cc1cc(O)c2ccccc2n1.O=P(Cl)(Cl)Cl
Cc1cc(Cl)c2ccccc2n1
null
null
null
Functional Group Interconversion
Alcohol to chloride_POCl3_para
27014e1419adc48e7dd5f2024d7f933bb85e42d4ec6c57e509da2884d477d689
e71580a8ffadb7b2717ecd7d68c1d3c0ca161ba5e6a787a49dad5a1359adc993
c1ccc2ncccc2c1
Cl-P(-Cl)(=O)-[Cl;H0;D1;+0:1].O-[c;H0;D3;+0:2]1:[c:3]:[c:4](-[C;D1;H3:5]):[#7;a:6]:[c:7](:[c:8]):[c:9]:1:[c:10]>>[C;D1;H3:5]-[c:4]1:[#7;a:6]:[c:7](:[c:8]):[c:9](:[c:10]):[c;H0;D3;+0:2](-[Cl;H0;D1;+0:1]):[c:3]:1
null
[]
null
null
30
MINUTE
Phosphorus oxychloride (30 mL) was added to 4-hydroxy-2-methylquinoline (10 g), and the mixture was stirred at room temperature for 30 min. The reaction mixture was concentrated under reduced pressure, and saturated aqueous sodium carbonate solution was added to the residue under ice-cooling. The mixture was extracted ...
10.6084/m9.figshare.5104873.v1
null
Aromatic alcohol
Aromatic halide
c1ccc2ncccc2c1
c1ccc2ncccc2c1
c1ccc2ncccc2c1
HCl
null
null
0.5
Cc1cc(O)c2ccccc2n1.O=P(Cl)(Cl)Cl>>Cc1cc(Cl)c2ccccc2n1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-4ef913eea72040918018fad2ac95998a
FC(F)(F)c1cc(Cl)c2ccccc2n1.OCCNCCO>>OCCN(CCO)c1cc(C(F)(F)F)nc2ccccc12
N(CCO)CCO.ClC1=CC(=NC2=CC=CC=C12)C(F)(F)F>>OCCN(CCO)C1=CC(=NC2=CC=CC=C12)C(F)(F)F
Cl[c:8]1[cH:9][c:10]([C:11]([F:12])([F:13])[F:14])[n:15][c:16]2[cH:17][cH:18][cH:19][cH:20][c:21]12.[OH:1][CH2:2][CH2:3][NH:4][CH2:5][CH2:6][OH:7]>>[OH:1][CH2:2][CH2:3][N:4]([CH2:5][CH2:6][OH:7])[c:8]1[cH:9][c:10]([C:11]([F:12])([F:13])[F:14])[n:15][c:16]2[cH:17][cH:18][cH:19][cH:20][c:21]12
FC(F)(F)c1cc(Cl)c2ccccc2n1.OCCNCCO
OCCN(CCO)c1cc(C(F)(F)F)nc2ccccc12
null
null
[Cl-].[Na+].O
Heteroatom Alkylation and Arylation
Ullmann-Goldberg Substitution amine
58b519bcefc8b0884f30564d454d0bf8e19d1792705c71f74402c97f0a6633f3
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
c1ccc2ncccc2c1
Cl-[c;H0;D3;+0:1]1:[c:2]:[c:3](-[C:4](-[F;D1;H0:5])(-[F;D1;H0:6])-[F;D1;H0:7]):[#7;a:8]:[c:9](:[c:10]):[c:11]:1:[c:12].[C:13]-[C:14]-[NH;D2;+0:15]-[C:16]-[C:17]>>[C:13]-[C:14]-[N;H0;D3;+0:15](-[C:16]-[C:17])-[c;H0;D3;+0:1]1:[c:2]:[c:3](-[C:4](-[F;D1;H0:5])(-[F;D1;H0:6])-[F;D1;H0:7]):[#7;a:8]:[c:9](:[c:10]):[c:11]:1:[c:...
null
[]
80
CELSIUS
19
HOUR
Diethanolamine (20 mL) was added to 4-chloro-2-trifluoromethylquinoline (5.04 g), and the mixture was stirred at 80° C. for 19 hr. Brine was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was dried and concentrated under reduced pressure. The residue was purified by silica ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
c1ccc2ncccc2c1
c1ccc2ncccc2c1
c1ccc2ncccc2c1
HCl
[Cl-].[Na+].O
80
19
FC(F)(F)c1cc(Cl)c2ccccc2n1.OCCNCCO>[Cl-].[Na+].O>OCCN(CCO)c1cc(C(F)(F)F)nc2ccccc12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-e74ad20a28894c1bbbb6389949431e49
CC(C)(C)OC(=O)N1C[C@@H](N2CCN(c3cc(C(N)=O)nc4ccccc34)CC2)C[C@H]1C(=O)N1CCSC1.Cl>>Cl.NC(=O)c1cc(N2CCN([C@@H]3CN[C@H](C(=O)N4CCSC4)C3)CC2)c2ccccc2n1
C(C)(C)(C)OC(=O)N1[C@@H](C[C@@H](C1)N1CCN(CC1)C1=CC(=NC2=CC=CC=C12)C(N)=O)C(=O)N1CSCC1.Cl.Cl.Cl.COC(=O)C1=NC2=CC=CC=C2C(=C1)N1CCN(CC1)[C@H]1C[C@H](NC1)C(=O)N1CSCC1>>Cl.Cl.Cl.C(N)(=O)C1=NC2=CC=CC=C2C(=C1)N1CCN(CC1)[C@H]1C[C@H](NC1)C(=O)N1CSCC1
CC(C)(C)OC(=O)[N:16]1[CH2:15][C@@H:14]([N:13]2[CH2:12][CH2:11][N:10]([c:9]3[cH:8][c:7]([C:5]([NH2:4])=[O:6])[n:34][c:33]4[c:28]3[cH:29][cH:30][cH:31][cH:32]4)[CH2:27][CH2:26]2)[CH2:25][C@H:17]1[C:18](=[O:19])[N:20]1[CH2:21][CH2:22][S:23][CH2:24]1.[ClH:3]>>[ClH:3].[NH2:4][C:5](=[O:6])[c:7]1[cH:8][c:9]([N:10]2[CH2:11][CH...
CC(C)(C)OC(=O)N1C[C@@H](N2CCN(c3cc(C(N)=O)nc4ccccc34)CC2)C[C@H]1C(=O)N1CCSC1.Cl
Cl.NC(=O)c1cc(N2CCN([C@@H]3CN[C@H](C(=O)N4CCSC4)C3)CC2)c2ccccc2n1
null
null
null
Miscellaneous
OtherReaction
f8d276f6195a26b4ed25eb5f7dc89f1f5d8836bc1a35a891d3ddc666caa9552d
c95e79e18f8ea11cf22745e0eab38cab98566b1b63e7d80ee200f4cb4f94f00c
O=C([C@@H]1C[C@H](N2CCN(c3ccnc4ccccc34)CC2)CN1)N1CCSC1
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1]1-[C:2]-[C:3]-[C:4]-[C:5]-1-[C:6](=[O;D1;H0:7])-[#7:8](-[C:9])-[C:10]-[#16:11]>>[#16:11]-[C:10]-[#7:8](-[C:6](=[O;D1;H0:7])-[C:5]1-[C:4]-[C:3]-[C:2]-[NH;D2;+0:1]-1)-[C:9]
null
[]
null
null
null
null
Using 3-{(2S,4S)-1-tert-butoxycarbonyl-4-[4-(2-carbamoyl-4-quinolyl)-1-piperazinyl]-2-pyrrolidinylcarbonyl}-1,3-thiazolidine [product of Example 262 (3), 1.05 g], and in the same manner as in Example 186 (2), the title compound (696 mg) was obtained as a brown powder. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Secondary amine
C1CC[NH]C1
C1CCNC1
C1C[NH]CC[NH]1.C1CCNC1.C1CSC[NH]1.c1ccc2ncccc2c1
HO-
null
null
null
CC(C)(C)OC(=O)N1C[C@@H](N2CCN(c3cc(C(N)=O)nc4ccccc34)CC2)C[C@H]1C(=O)N1CCSC1.Cl>>Cl.NC(=O)c1cc(N2CCN([C@@H]3CN[C@H](C(=O)N4CCSC4)C3)CC2)c2ccccc2n1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-eb5a3fd241214b508b2809001144e82b
CCOC=C(C(=O)OCC)C(=O)OCC.Nc1ccccc1>>CCOC(=O)c1cnc2ccccc2c1O
C(C)OC=C(C(=O)OCC)C(=O)OCC.NC1=CC=CC=C1>>OC1=C(C=NC2=CC=CC=C12)C(=O)OCC
CCO[CH:7]=[C:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[C:15](OCC)=[O:16].[NH2:8][c:9]1[cH:10][cH:11][cH:12][cH:13][cH:14]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][n:8][c:9]2[cH:10][cH:11][cH:12][cH:13][c:14]2[c:15]1[OH:16]
CCOC=C(C(=O)OCC)C(=O)OCC.Nc1ccccc1
CCOC(=O)c1cnc2ccccc2c1O
null
null
null
Aromatic Heterocycle Formation
OtherReaction
e04d5084bd6bde4efb79456fdff70fdac6e2cf2829400707e635c879cfe5d271
4a985e8b872e7ba2e4af89799e804f05fef7f2382ed6af4bf801b35cf0e038a9
c1ccc2ncccc2c1
C-C-O-[CH;D2;+0:1]=[C;H0;D3;+0:2](-[C:3](=[O;D1;H0:4])-[#8:5]-[C:6])-[C;H0;D3;+0:7](=[O;H0;D1;+0:8])-O-C-C.[NH2;D1;+0:9]-[c:10](:[c:11]):[cH;D2;+0:12]:[c:13]:[c:14]>>[C:6]-[#8:5]-[C:3](=[O;D1;H0:4])-[c;H0;D3;+0:2]1:[cH;D2;+0:1]:[n;H0;D2;+0:9]:[c:10](:[c:11]):[c;H0;D3;+0:12](:[c:13]:[c:14]):[c;H0;D3;+0:7]:1-[OH;D1;+0:8]
44.1
[{"value": 44.1, "product": "OC1=C(C=NC2=CC=CC=C12)C(=O)OCC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
200
CELSIUS
2
HOUR
Diethyl ethoxymethylenemalonate (115 g) was dropwise added to aniline (50 g), and the mixture was refluxed for 1 hr. The resulting ethanol was evaporated under atmospheric pressure, and the residue was heated at 200° C. and poured into diphenyl ether (750 mL). The mixture was stirred at 220-250° C. for 2 hr with heatin...
10.6084/m9.figshare.5104873.v1
null
Ester.Ester.Ether.Primary amine
Ester.Aromatic alcohol
c1ccccc1
c1ccc2ncccc2c1
c1ccc2ncccc2c1
HO-
null
200
2
CCOC=C(C(=O)OCC)C(=O)OCC.Nc1ccccc1>>CCOC(=O)c1cnc2ccccc2c1O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-ce7bfe590e3a4a64a00c07b68f3053f5
NC(=O)c1cc(Cl)c2ccccc2n1>>Nc1cc(Cl)c2ccccc2n1
ClC1=CC(=NC2=CC=CC=C12)C(=O)N.Cl.Cl.Cl.COC(=O)C1=NC2=CC=CC=C2C(=C1)N1CCN(CC1)[C@H]1C[C@H](NC1)C(=O)N1CSCC1.BrBr>>NC1=NC2=CC=CC=C2C(=C1)Cl
O=[C:2](c1[cH:3][c:4]([Cl:5])[c:6]2[cH:7][cH:8][cH:9][cH:10][c:11]2[n:12]1)[NH2:1]>>[NH2:1][c:2]1[cH:3][c:4]([Cl:5])[c:6]2[cH:7][cH:8][cH:9][cH:10][c:11]2[n:12]1
NC(=O)c1cc(Cl)c2ccccc2n1
Nc1cc(Cl)c2ccccc2n1
null
null
O1CCCC1.[OH-].[K+]
Miscellaneous
OtherReaction
db13421ac872302695d3ef4c6aa1985fa1af435b90dfc9e11f331be76489d7d2
49d40a8831465b2291100ac78f3ed653b3694eee3493e3566de3b9018d8cc734
c1ccc2ncccc2c1
O=[C;H0;D3;+0:1](-[N;D1;H2:2])-c1:[cH;D2;+0:3]:[c:4](-[Cl;D1;H0:5]):[c:6]:[c:7](:[c:8]):[n;H0;D2;+0:9]:1>>[Cl;D1;H0:5]-[c:4]1:[c:6]:[c:7](:[c:8]):[n;H0;D2;+0:9]:[c;H0;D3;+0:1](-[N;D1;H2:2]):[cH;D2;+0:3]:1
null
[]
null
null
30
MINUTE
Bromine (2.32 mL) was dissolved in 5% aqueous potassium hydroxide solution (190 mL), and a solution of 4-chloroquinoline-2-carboxamide [product of Example 262 (1), 9.80 g] in tetrahydrofuran (190 mL) was dropwise added thereto. The mixture was stirred at room temperature for 30 min, and the mixture was stirred at 80° C...
10.6084/m9.figshare.5104873.v1
null
Primary amide
null
c1ccc2ncccc2c1
c1ccc2ncccc2c1
c1ccc2ncccc2c1
Other
O1CCCC1.[OH-].[K+]
null
0.5
NC(=O)c1cc(Cl)c2ccccc2n1>O1CCCC1.[OH-].[K+]>Nc1cc(Cl)c2ccccc2n1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-816c337a791d4fc79493c67e92e65e50
C1CNCCN1.Clc1ccc2c(Cl)ccnc2c1>>Clc1ccc2c(N3CCNCC3)ccnc2c1
N1CCNCC1.ClC1=CC=NC2=CC(=CC=C12)Cl>>ClC1=CC=C2C(=CC=NC2=C1)N1CCNCC1
[NH:7]1[CH2:8][CH2:9][NH:10][CH2:11][CH2:12]1.Cl[c:6]1[c:5]2[cH:4][cH:3][c:2]([Cl:1])[cH:17][c:16]2[n:15][cH:14][cH:13]1>>[Cl:1][c:2]1[cH:3][cH:4][c:5]2[c:6]([N:7]3[CH2:8][CH2:9][NH:10][CH2:11][CH2:12]3)[cH:13][cH:14][n:15][c:16]2[cH:17]1
C1CNCCN1.Clc1ccc2c(Cl)ccnc2c1
Clc1ccc2c(N3CCNCC3)ccnc2c1
null
null
O
Heteroatom Alkylation and Arylation
Ullmann-Goldberg Substitution amine
3fbb016f359467d4eec60eb9e91655d372a48980ac0112856b33886c38619450
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
c1ccc2c(N3CCNCC3)ccnc2c1
Cl-[c;H0;D3;+0:1]1:[c:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#7:9]1-[C:10]-[C:11]-[NH;D2;+0:12]-[C:13]-[C:14]-1>>[c:6]:[c:5]1:[#7;a:4]:[c:3]:[c:2]:[c;H0;D3;+0:1](-[N;H0;D3;+0:12]2-[C:11]-[C:10]-[#7:9]-[C:14]-[C:13]-2):[c:7]:1:[c:8]
41.1
[{"value": 41.1, "product": "ClC1=CC=C2C(=CC=NC2=C1)N1CCNCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
120
CELSIUS
2.5
HOUR
Piperazine (65.2 g) was melted by heating at 120° C., and 4,7-dichloroquinoline (15.0 g) was added thereto. The mixture was stirred at 120° C. for 2.5 hr and the reaction mixture was added to water. The mixture was extracted with chloroform and concentrated under reduced pressure to give 1-(7-chloro-4-quinolyl)piperazi...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CNCCN1.c1ccc2ncccc2c1
C1C[NH]CCN1.c1ccc2ncccc2c1
C1C[NH]CCN1.c1ccc2ncccc2c1
HCl
O
120
2.5
C1CNCCN1.Clc1ccc2c(Cl)ccnc2c1>O>Clc1ccc2c(N3CCNCC3)ccnc2c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-8a786ded399443c7afc06d6e8649e3ce
CCOC(=O)CC(=O)C(F)(F)F.Cc1ccccc1N>>Cc1cccc2c(O)cc(C(F)(F)F)nc12
CC1=C(N)C=CC=C1.FC(C(CC(=O)OCC)=O)(F)F.O>>FC(C1=NC2=C(C=CC=C2C(=C1)O)C)(F)F
CCO[C:7](=[O:8])[CH2:9][C:10](=O)[C:11]([F:12])([F:13])[F:14].[CH3:1][c:2]1[cH:3][cH:4][cH:5][cH:6][c:16]1[NH2:15]>>[CH3:1][c:2]1[cH:3][cH:4][cH:5][c:6]2[c:7]([OH:8])[cH:9][c:10]([C:11]([F:12])([F:13])[F:14])[n:15][c:16]12
CCOC(=O)CC(=O)C(F)(F)F.Cc1ccccc1N
Cc1cccc2c(O)cc(C(F)(F)F)nc12
null
null
P(O)(O)(O)=O
Aromatic Heterocycle Formation
OtherReaction
03fb309d467457208d11accffba771ac71177021179459bf0cc1e729b7f7524b
e4cbab44abd9117eb42f959793b157d31b1dce9de3f9c3954c67bf975e572e43
c1ccc2ncccc2c1
C-C-O-[C;H0;D3;+0:1](=[O;H0;D1;+0:2])-[CH2;D2;+0:3]-[C;H0;D3;+0:4](=O)-[C:5](-[F;D1;H0:6])(-[F;D1;H0:7])-[F;D1;H0:8].[NH2;D1;+0:9]-[c:10](:[c:11]):[cH;D2;+0:12]:[c:13]:[c:14]>>[F;D1;H0:6]-[C:5](-[F;D1;H0:7])(-[F;D1;H0:8])-[c;H0;D3;+0:4]1:[cH;D2;+0:3]:[c;H0;D3;+0:1](-[OH;D1;+0:2]):[c;H0;D3;+0:12](:[c:13]:[c:14]):[c:10](...
17.4
[{"value": 17.4, "product": "FC(C1=NC2=C(C=CC=C2C(=C1)O)C)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
105
CELSIUS
5.5
HOUR
2-Methylaniline (5.00 g) was dissolved in 75% phosphoric acid (20 mL), and ethyl trifluoroacetoacetate (8.60 g) was dropwise added thereto at 105° C. The mixture was stirred at 105° C. for 5.5 hr. After allowing to cool, the reaction mixture was added to water. The precipitated solid was collected by filtration to give...
10.6084/m9.figshare.5104873.v1
null
Ketone.Ester.Primary amine
Aromatic alcohol
c1ccccc1
c1ccc2ncccc2c1
c1ccc2ncccc2c1
HO-
P(O)(O)(O)=O
105
5.5
CCOC(=O)CC(=O)C(F)(F)F.Cc1ccccc1N>P(O)(O)(O)=O>Cc1cccc2c(O)cc(C(F)(F)F)nc12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-aaeb23c7d47e4c37afe76145535b2e03
O=P(Cl)(Cl)Cl.Oc1cc(C(F)(F)F)nc2ccc(C(F)(F)F)cc12>>FC(F)(F)c1ccc2nc(C(F)(F)F)cc(Cl)c2c1
OC1=CC(=NC2=CC=C(C=C12)C(F)(F)F)C(F)(F)F.P(=O)(Cl)(Cl)Cl>>ClC1=CC(=NC2=CC=C(C=C12)C(F)(F)F)C(F)(F)F
O=P(Cl)(Cl)[Cl:17].O[c:16]1[cH:15][c:10]([C:11]([F:12])([F:13])[F:14])[n:9][c:8]2[cH:7][cH:6][c:5]([C:2]([F:1])([F:3])[F:4])[cH:19][c:18]21>>[F:1][C:2]([F:3])([F:4])[c:5]1[cH:6][cH:7][c:8]2[n:9][c:10]([C:11]([F:12])([F:13])[F:14])[cH:15][c:16]([Cl:17])[c:18]2[cH:19]1
O=P(Cl)(Cl)Cl.Oc1cc(C(F)(F)F)nc2ccc(C(F)(F)F)cc12
FC(F)(F)c1ccc2nc(C(F)(F)F)cc(Cl)c2c1
null
null
null
Functional Group Interconversion
Alcohol to chloride_POCl3_para
27014e1419adc48e7dd5f2024d7f933bb85e42d4ec6c57e509da2884d477d689
e71580a8ffadb7b2717ecd7d68c1d3c0ca161ba5e6a787a49dad5a1359adc993
c1ccc2ncccc2c1
Cl-P(-Cl)(=O)-[Cl;H0;D1;+0:1].O-[c;H0;D3;+0:2]1:[c:3]:[c:4](-[C:5](-[F;D1;H0:6])(-[F;D1;H0:7])-[F;D1;H0:8]):[#7;a:9]:[c:10](:[c:11]):[c:12]:1:[c:13]>>[Cl;H0;D1;+0:1]-[c;H0;D3;+0:2]1:[c:3]:[c:4](-[C:5](-[F;D1;H0:6])(-[F;D1;H0:7])-[F;D1;H0:8]):[#7;a:9]:[c:10](:[c:11]):[c:12]:1:[c:13]
null
[]
null
null
17
HOUR
4-Hydroxy-2,6-bis(trifluoromethyl)quinoline (1.28 g) was dissolved in phosphorus oxychloride (5.0 mL), and the mixture was stirred at room temperature for 17 hr. The reaction mixture was concentrated under reduced pressure, and saturated aqueous sodium hydrogencarbonate solution was added to the residue. The mixture wa...
10.6084/m9.figshare.5104873.v1
null
Aromatic alcohol
Aromatic halide
c1ccc2ncccc2c1
c1ccc2ncccc2c1
c1ccc2ncccc2c1
HCl
null
null
17
O=P(Cl)(Cl)Cl.Oc1cc(C(F)(F)F)nc2ccc(C(F)(F)F)cc12>>FC(F)(F)c1ccc2nc(C(F)(F)F)cc(Cl)c2c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-8809f565982e48bd9ed66429e37203cc
CCOC(=O)CC(=O)C(F)(F)F.COc1ccc(N)cc1>>COc1ccc2nc(C(F)(F)F)cc(O)c2c1
COC1=CC=C(N)C=C1.FC(C(CC(=O)OCC)=O)(F)F.C(O)([O-])=O.[Na+]>>FC(C1=NC2=CC=C(C=C2C(=C1)O)OC)(F)F
CCO[C:14]([CH2:13][C:8](=O)[C:9]([F:10])([F:11])[F:12])=[O:15].[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([NH2:7])[cH:16][cH:17]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[n:7][c:8]([C:9]([F:10])([F:11])[F:12])[cH:13][c:14]([OH:15])[c:16]2[cH:17]1
CCOC(=O)CC(=O)C(F)(F)F.COc1ccc(N)cc1
COc1ccc2nc(C(F)(F)F)cc(O)c2c1
null
null
P(O)(O)(O)=O
Aromatic Heterocycle Formation
OtherReaction
03fb309d467457208d11accffba771ac71177021179459bf0cc1e729b7f7524b
e4cbab44abd9117eb42f959793b157d31b1dce9de3f9c3954c67bf975e572e43
c1ccc2ncccc2c1
C-C-O-[C;H0;D3;+0:1](=[O;H0;D1;+0:2])-[CH2;D2;+0:3]-[C;H0;D3;+0:4](=O)-[C:5](-[F;D1;H0:6])(-[F;D1;H0:7])-[F;D1;H0:8].[NH2;D1;+0:9]-[c:10](:[c:11]):[cH;D2;+0:12]:[c:13]:[c:14]>>[F;D1;H0:6]-[C:5](-[F;D1;H0:7])(-[F;D1;H0:8])-[c;H0;D3;+0:4]1:[cH;D2;+0:3]:[c;H0;D3;+0:1](-[OH;D1;+0:2]):[c;H0;D3;+0:12](:[c:13]:[c:14]):[c:10](...
4.6
[{"value": 4.6, "product": "FC(C1=NC2=CC=C(C=C2C(=C1)O)OC)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
110
CELSIUS
4
HOUR
4-Methoxyaniline (5.00 g) was dissolved in 75% phosphoric acid (20 mL) and ethyl trifluoroacetoacetate (7.48 g) was dropwise added thereto at 110° C. The mixture was stirred at 110° C. for 4 hr with heating. After allowing to cool, the reaction mixture was added to saturated aqueous sodium hydrogencarbonate solution, a...
10.6084/m9.figshare.5104873.v1
null
Ketone.Ester.Primary amine
Aromatic alcohol
c1ccccc1
c1ccc2ncccc2c1
c1ccc2ncccc2c1
HO-
P(O)(O)(O)=O
110
4
CCOC(=O)CC(=O)C(F)(F)F.COc1ccc(N)cc1>P(O)(O)(O)=O>COc1ccc2nc(C(F)(F)F)cc(O)c2c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-536255495e2a44b2857c9407963d2f6a
CCOC(=O)CC(=O)C(F)(F)F.Nc1ccccc1F>>Oc1cc(C(F)(F)F)nc2c(F)cccc12
FC1=C(N)C=CC=C1.FC(C(CC(=O)OCC)=O)(F)F.Cl>>FC=1C=CC=C2C(=CC(=NC12)C(F)(F)F)O
CCO[C:2](=[O:1])[CH2:3][C:4](=O)[C:5]([F:6])([F:7])[F:8].[NH2:9][c:10]1[c:11]([F:12])[cH:13][cH:14][cH:15][cH:16]1>>[OH:1][c:2]1[cH:3][c:4]([C:5]([F:6])([F:7])[F:8])[n:9][c:10]2[c:11]([F:12])[cH:13][cH:14][cH:15][c:16]12
CCOC(=O)CC(=O)C(F)(F)F.Nc1ccccc1F
Oc1cc(C(F)(F)F)nc2c(F)cccc12
null
null
C1=CC=CC=C1
Aromatic Heterocycle Formation
OtherReaction
03fb309d467457208d11accffba771ac71177021179459bf0cc1e729b7f7524b
e4cbab44abd9117eb42f959793b157d31b1dce9de3f9c3954c67bf975e572e43
c1ccc2ncccc2c1
C-C-O-[C;H0;D3;+0:1](=[O;H0;D1;+0:2])-[CH2;D2;+0:3]-[C;H0;D3;+0:4](=O)-[C:5](-[F;D1;H0:6])(-[F;D1;H0:7])-[F;D1;H0:8].[NH2;D1;+0:9]-[c:10](:[c:11]):[cH;D2;+0:12]:[c:13]:[c:14]>>[F;D1;H0:6]-[C:5](-[F;D1;H0:7])(-[F;D1;H0:8])-[c;H0;D3;+0:4]1:[cH;D2;+0:3]:[c;H0;D3;+0:1](-[OH;D1;+0:2]):[c;H0;D3;+0:12](:[c:13]:[c:14]):[c:10](...
8.5
[{"value": 8.5, "product": "FC=1C=CC=C2C(=CC(=NC12)C(F)(F)F)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
110
CELSIUS
5
HOUR
2-Fluoroaniline (10.0 g), ethyl trifluoroacetoacetate (16.6 g) and concentrated hydrochloric acid (0.1 mL) were dissolved in benzene (40 mL), and the mixture was refluxed in a reaction vessel equipped with Dean-Stark trap for 7 hr. The reaction mixture was concentrated under reduced pressure and 75% phosphoric acid (40...
10.6084/m9.figshare.5104873.v1
null
Ketone.Ester.Primary amine
Aromatic alcohol
c1ccccc1
c1ccc2ncccc2c1
c1ccc2ncccc2c1
HO-
C1=CC=CC=C1
110
5
CCOC(=O)CC(=O)C(F)(F)F.Nc1ccccc1F>C1=CC=CC=C1>Oc1cc(C(F)(F)F)nc2c(F)cccc12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-e297209212a341e9b02c2b927f4d1f4b
Oc1ncc(Br)c2ccccc12.[C-]#N>>N#Cc1cnc(O)c2ccccc12
BrC1=CN=C(C2=CC=CC=C12)O.[Cu](C#N)C#N.[C-]#N.[Na+]>>C(#N)C1=CN=C(C2=CC=CC=C12)O
Br[c:3]1[cH:4][n:5][c:6]([OH:7])[c:8]2[cH:9][cH:10][cH:11][cH:12][c:13]12.[N:1]#[C-:2]>>[N:1]#[C:2][c:3]1[cH:4][n:5][c:6]([OH:7])[c:8]2[cH:9][cH:10][cH:11][cH:12][c:13]12
Oc1ncc(Br)c2ccccc12.[C-]#N
N#Cc1cnc(O)c2ccccc12
null
null
null
C-C Coupling
OtherReaction
92707350c198f3a27d317e8fa64c689eac735ee51a37176521f223f0bfcebd15
2549b026e730aedabd9d1c88337e10b7987bb7b86597cabf3fd7fef1a79c8a9a
c1ccc2cnccc2c1
Br-[c;H0;D3;+0:1]1:[c:2]:[#7;a:3]:[c:4]:[c:5]:[c:6]:1:[c:7].[C-;H0;D1:8]#[N;D1;H0:9]>>[N;D1;H0:9]#[C;H0;D2;+0:8]-[c;H0;D3;+0:1]1:[c:2]:[#7;a:3]:[c:4]:[c:5]:[c:6]:1:[c:7]
52.3
[{"value": 52.3, "product": "C(#N)C1=CN=C(C2=CC=CC=C12)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
180
CELSIUS
4
HOUR
4-Bromo-1-hydroxyisoquinoline (1.56 g) was dissolved in N-methyl-2-pyrrolidine (25 mL), and copper cyanide (1.56 g) was added thereto. The mixture was stirred at 180° C. for 4 hr with heating. The reaction mixture was added to cool to 100° C. and added to an aqueous solution (125 mL) of sodium cyanide (31.25 g). The mi...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
Nitrile
c1ccc2cnccc2c1
c1ccc2cnccc2c1
c1ccc2cnccc2c1
Br-
null
180
4
Oc1ncc(Br)c2ccccc12.[C-]#N>>N#Cc1cnc(O)c2ccccc12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-892bf58bc5f249259d29bc6954817092
C1CNCCN1.Clc1nc(-c2ccccc2)nc2ccccc12>>c1ccc(-c2nc(N3CCNCC3)c3ccccc3n2)cc1
N1CCNCC1.ClC1=NC(=NC2=CC=CC=C12)C1=CC=CC=C1>>C1(=CC=CC=C1)C1=NC2=CC=CC=C2C(=N1)N1CCNCC1
[NH:8]1[CH2:9][CH2:10][NH:11][CH2:12][CH2:13]1.Cl[c:7]1[n:6][c:5](-[c:4]2[cH:3][cH:2][cH:1][cH:22][cH:21]2)[n:20][c:19]2[c:14]1[cH:15][cH:16][cH:17][cH:18]2>>[cH:1]1[cH:2][cH:3][c:4](-[c:5]2[n:6][c:7]([N:8]3[CH2:9][CH2:10][NH:11][CH2:12][CH2:13]3)[c:14]3[cH:15][cH:16][cH:17][cH:18][c:19]3[n:20]2)[cH:21][cH:22]1
C1CNCCN1.Clc1nc(-c2ccccc2)nc2ccccc12
c1ccc(-c2nc(N3CCNCC3)c3ccccc3n2)cc1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Ullmann-Goldberg Substitution amine
f13699ff5146e0568096477cb3cce45c70a67b236ed45674e8779117004a8dcf
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
c1ccc(-c2nc(N3CCNCC3)c3ccccc3n2)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].[#7:9]1-[C:10]-[C:11]-[NH;D2;+0:12]-[C:13]-[C:14]-1>>[c:8]:[c:7]1:[c:5](:[c:6]):[#7;a:4]:[c:3]:[#7;a:2]:[c;H0;D3;+0:1]:1-[N;H0;D3;+0:12]1-[C:13]-[C:14]-[#7:9]-[C:10]-[C:11]-1
62.7
[{"value": 62.7, "product": "C1(=CC=CC=C1)C1=NC2=CC=CC=C2C(=N1)N1CCNCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
6
HOUR
Piperazine (3.22 g) was dissolved in DMF (830 mL), and 4-chloro-2-phenylquinazoline (3 g) was added thereto. The mixture was stirred at room temperature for 6 hr. The reaction mixture was concentrated under reduced pressure, water and chloroform were added to the residue and an insoluble material was filtered off. The ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CNCCN1.c1ccc2ncncc2c1
C1C[NH]CCN1.c1ccc2ncncc2c1
c1ccccc1.C1C[NH]CCN1.c1ccc2ncncc2c1
HCl
CN(C)C=O
null
6
C1CNCCN1.Clc1nc(-c2ccccc2)nc2ccccc12>CN(C)C=O>c1ccc(-c2nc(N3CCNCC3)c3ccccc3n2)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-7b0f1f72213e420485430ea327cd8215
N#Cc1ccncc1.[Cl-].[NH4+]>>Cl.N=C(N)c1ccncc1
CC(=O)C.C(#N)C1=CC=NC=C1.C[O-].[Na+].CO.[Cl-].[NH4+]>>Cl.C(N)(=N)C1=CC=NC=C1
[N:2]#[C:3][c:5]1[cH:6][cH:7][n:8][cH:9][cH:10]1.[Cl-:1].[NH4+:4]>>[ClH:1].[NH:2]=[C:3]([NH2:4])[c:5]1[cH:6][cH:7][n:8][cH:9][cH:10]1
N#Cc1ccncc1.[Cl-].[NH4+]
Cl.N=C(N)c1ccncc1
null
null
CO
Functional Group Interconversion
OtherReaction
3b047a13c16a607c445b1c419e256808e8c9a0097d8fb9efd4e7970deb782b70
2882e57127fc469aa16ca9a2fd53388b6d97c74c76c010e6eb01be5726f46aa5
c1ccncc1
[Cl-;H0;D0:1].[N;H0;D1;+0:2]#[C;H0;D2;+0:3]-[c:4]1:[c:5]:[c:6]:[#7;a:7]:[c:8]:[c:9]:1.[NH4+;D0:10]>>[ClH;D0;+0:1].[NH2;D1;+0:10]-[C;H0;D3;+0:3](=[NH;D1;+0:2])-[c:4]1:[c:5]:[c:6]:[#7;a:7]:[c:8]:[c:9]:1
83
[{"value": 83.0, "product": "Cl.C(N)(=N)C1=CC=NC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
15
MINUTE
4-Cyanopyridine (50.0 g) was suspended in methanol (50 mL), and 28% sodium methoxide-methanol solution (4.14 mL) was added thereto. After stirring at room temperature for 15 min, ammonium chloride (25.7 g) was added to the mixture. The mixture was stirred at room temperature for 24 hr. Acetone (200 mL) was added to the...
10.6084/m9.figshare.5104873.v1
null
Nitrile
Primary amine
null
null
c1ccncc1
null
CO
null
0.25
N#Cc1ccncc1.[Cl-].[NH4+]>CO>Cl.N=C(N)c1ccncc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-d863b73c392e4aa7ab2a5db34021dbe8
NC(=O)C1CCNCC1.O=C(Cl)OOCc1ccccc1>>NC(=O)C1CCN(C(=O)OCc2ccccc2)CC1
C(O)([O-])=O.[Na+].N1CCC(C(=O)N)CC1.C(C)N(CC)CC.C(OOCC1=CC=CC=C1)(=O)Cl>>C(C1=CC=CC=C1)OC(=O)N1CCC(CC1)C(N)=O
[NH2:1][C:2](=[O:3])[CH:4]1[CH2:5][CH2:6][NH:7][CH2:18][CH2:19]1.Cl[C:8](O[O:10][CH2:11][c:12]1[cH:13][cH:14][cH:15][cH:16][cH:17]1)=[O:9]>>[NH2:1][C:2](=[O:3])[CH:4]1[CH2:5][CH2:6][N:7]([C:8](=[O:9])[O:10][CH2:11][c:12]2[cH:13][cH:14][cH:15][cH:16][cH:17]2)[CH2:18][CH2:19]1
NC(=O)C1CCNCC1.O=C(Cl)OOCc1ccccc1
NC(=O)C1CCN(C(=O)OCc2ccccc2)CC1
null
null
ClCCl
Protection
OtherReaction
9b3e16e3365fc2aab67381996da7bc0ea1118efbb735841432d91d1d6fbc92af
6bd83aa074f5ddfdc0cbd04384f2ba85b7424fcae0840640aecc60fd7897d28c
O=C(OCc1ccccc1)N1CCCCC1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-O-[O;H0;D2;+0:3]-[C:4]-[c:5].[C:6]-[C:7]-[NH;D2;+0:8]-[C:9]-[C:10]>>[C:6]-[C:7]-[N;H0;D3;+0:8](-[C;H0;D3;+0:1](=[O;D1;H0:2])-[O;H0;D2;+0:3]-[C:4]-[c:5])-[C:9]-[C:10]
null
[]
null
null
18
HOUR
Isonipecotamide (19.4 g) and triethylamine (42 mL) were dissolved in dichloromethane (500 mL), and benzyloxy chlorocarbonate (24 mL) was added thereto under ice-cooling. The mixture was stirred at room temperature for 18 hr. The reaction mixture was added to saturated aqueous sodium hydrogencarbonate solution, and the ...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Secondary amine.Peroxide
Carbamic ester
C1CCNCC1
C1CC[NH]CC1
C1CC[NH]CC1.c1ccccc1
HCl
ClCCl
null
18
NC(=O)C1CCNCC1.O=C(Cl)OOCc1ccccc1>ClCCl>NC(=O)C1CCN(C(=O)OCc2ccccc2)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-14f11ccce1a74aa28b695244722b3993
CCO.N#CC1CCN(C(=O)OCc2ccccc2)CC1>>CCOC(=N)C1CCN(C(=O)OCc2ccccc2)CC1
C(C)(=O)Cl.C(C)O.C(C1=CC=CC=C1)OC(=O)N1CCC(CC1)C#N.Cl.Cl.C(C)(C)(C)N1N=C(N=N1)C1CCN(CC1)[C@H]1C[C@H](NC1)C(=O)N1CSCC1>>Cl.C(C1=CC=CC=C1)OC(=O)N1CCC(CC1)C(=N)OCC
[CH3:1][CH2:2][OH:3].[C:4](#[N:5])[CH:6]1[CH2:7][CH2:8][N:9]([C:10](=[O:11])[O:12][CH2:13][c:14]2[cH:15][cH:16][cH:17][cH:18][cH:19]2)[CH2:20][CH2:21]1>>[CH3:1][CH2:2][O:3][C:4](=[NH:5])[CH:6]1[CH2:7][CH2:8][N:9]([C:10](=[O:11])[O:12][CH2:13][c:14]2[cH:15][cH:16][cH:17][cH:18][cH:19]2)[CH2:20][CH2:21]1
CCO.N#CC1CCN(C(=O)OCc2ccccc2)CC1
CCOC(=N)C1CCN(C(=O)OCc2ccccc2)CC1
null
null
C(Cl)(Cl)Cl
Acylation
OtherReaction
e564e96d7d2f965b49edf364feccacb527e51024ce8a97adfccc27d77cbffea1
515b5097d48e8822f99e612a636ab28d5c6d3dcc515412839570278fb17e2efd
O=C(OCc1ccccc1)N1CCCCC1
[C;D1;H3:1]-[C:2]-[OH;D1;+0:3].[C:4]-[C:5](-[C;H0;D2;+0:6]#[N;H0;D1;+0:7])-[C:8]>>[C:4]-[C:5](-[C;H0;D3;+0:6](=[NH;D1;+0:7])-[O;H0;D2;+0:3]-[C:2]-[C;D1;H3:1])-[C:8]
null
[]
null
null
30
MINUTE
Acetyl chloride (180 mL) was dropwise added to a mixture of ethanol (160 mL) and chloroform (180 mL) under ice-cooling. After the mixture was stirred for 30 min, a solution of 1-benzyloxycarbonyl-4-cyanopiperidine [product of Example 298 (2), 20.6 g] in chloroform (180 mL) was added thereto under ice-cooling. The mixtu...
10.6084/m9.figshare.5104873.v1
null
Nitrile.Primary alcohol
Ether
null
null
C1CC[NH]CC1.c1ccccc1
null
C(Cl)(Cl)Cl
null
0.5
CCO.N#CC1CCN(C(=O)OCc2ccccc2)CC1>C(Cl)(Cl)Cl>CCOC(=N)C1CCN(C(=O)OCc2ccccc2)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-139a19a6f6bb445a83961b53fe14abaf
CCOC(=O)c1ccc2oc(C3CCN([C@H]4C[C@@H](C(=O)N5CCSC5)N(C(=O)OC(C)(C)C)C4)CC3)nc2c1>>CC(C)(C)OC(=O)N1C[C@@H](N2CCC(c3nc4cc(C(=O)O)ccc4o3)CC2)C[C@H]1C(=O)N1CCSC1
O.[OH-].[Li+].C(C)(C)(C)OC(=O)N1[C@@H](C[C@@H](C1)N1CCC(CC1)C=1OC2=C(N1)C=C(C=C2)C(=O)OCC)C(=O)N2CSCC2.C(C)OC(=O)C=1C=CC2=C(N=C(O2)C2CCN(CC2)[C@H]2C[C@H](NC2)C(=O)N2CSCC2)C1>>C(C)(C)(C)OC(=O)N1[C@@H](C[C@@H](C1)N1CCC(CC1)C=1OC2=C(N1)C=C(C=C2)C(=O)O)C(=O)N2CSCC2
CC[O:22][C:20]([c:19]1[cH:18][c:17]2[n:16][c:15]([CH:14]3[CH2:13][CH2:12][N:11]([C@@H:10]4[CH2:9][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[C@H:30]([C:31](=[O:32])[N:33]5[CH2:34][CH2:35][S:36][CH2:37]5)[CH2:29]4)[CH2:28][CH2:27]3)[o:26][c:25]2[cH:24][cH:23]1)=[O:21]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6...
CCOC(=O)c1ccc2oc(C3CCN([C@H]4C[C@@H](C(=O)N5CCSC5)N(C(=O)OC(C)(C)C)C4)CC3)nc2c1
CC(C)(C)OC(=O)N1C[C@@H](N2CCC(c3nc4cc(C(=O)O)ccc4o3)CC2)C[C@H]1C(=O)N1CCSC1
null
null
Cl.O.C(C)O
Deprotection
Ester saponification (alkyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=C([C@@H]1C[C@H](N2CCC(c3nc4ccccc4o3)CC2)CN1)N1CCSC1
C-C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]>>[O;D1;H0:3]=[C:2](-[OH;D1;+0:1])-[c:4]
80.5
[{"value": 80.5, "product": "C(C)(C)(C)OC(=O)N1[C@@H](C[C@@H](C1)N1CCC(CC1)C=1OC2=C(N1)C=C(C=C2)C(=O)O)C(=O)N2CSCC2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3.5
HOUR
3-{(2S,4S)-1-tert-Butoxycarbonyl-4-[4-(5-ethoxycarbonyl-2 -benzoxazolyl)piperidino]-2-pyrrolidinylcarbonyl}-1,3-thiazolidine [product of Example 309 (3), 4.51 g] was dissolved in ethanol (16 mL) and water (8 mL), and lithium hydroxide monohydrate (678 mg) was added. The mixture was stirred at room temperature for 3.5 h...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
C1CC[NH]C1.C1CC[NH]CC1.c1ccc2ocnc2c1.C1CSC[NH]1
Other
Cl.O.C(C)O
null
3.5
CCOC(=O)c1ccc2oc(C3CCN([C@H]4C[C@@H](C(=O)N5CCSC5)N(C(=O)OC(C)(C)C)C4)CC3)nc2c1>Cl.O.C(C)O>CC(C)(C)OC(=O)N1C[C@@H](N2CCC(c3nc4cc(C(=O)O)ccc4o3)CC2)C[C@H]1C(=O)N1CCSC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-e5f8a227751f4bb0aad3aad7cf9cb409
CC(C)(C)OC(=O)N1C[C@@H](N2CCC(c3nc4cc(C(=O)O)ccc4o3)CC2)C[C@H]1C(=O)N1CCSC1.N>>CC(C)(C)OC(=O)N1C[C@@H](N2CCC(c3nc4cc(C(N)=O)ccc4o3)CC2)C[C@H]1C(=O)N1CCSC1
N.CO.C(C)(C)(C)OC(=O)N1[C@@H](C[C@@H](C1)N1CCC(CC1)C=1OC2=C(N1)C=C(C=C2)C(=O)O)C(=O)N2CSCC2.Cl.Cl.C(=O)(O)C=1C=CC2=C(N=C(O2)C2CCN(CC2)[C@H]2C[C@H](NC2)C(=O)N2CSCC2)C1.C(OCC(C)C)(=O)Cl>>C(C)(C)(C)OC(=O)N1[C@@H](C[C@@H](C1)N1CCC(CC1)C=1OC2=C(N1)C=C(C=C2)C(N)=O)C(=O)N2CSCC2
O[C:20]([c:19]1[cH:18][c:17]2[n:16][c:15]([CH:14]3[CH2:13][CH2:12][N:11]([C@@H:10]4[CH2:9][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[C@H:30]([C:31](=[O:32])[N:33]5[CH2:34][CH2:35][S:36][CH2:37]5)[CH2:29]4)[CH2:28][CH2:27]3)[o:26][c:25]2[cH:24][cH:23]1)=[O:22].[NH3:21]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C...
CC(C)(C)OC(=O)N1C[C@@H](N2CCC(c3nc4cc(C(=O)O)ccc4o3)CC2)C[C@H]1C(=O)N1CCSC1.N
CC(C)(C)OC(=O)N1C[C@@H](N2CCC(c3nc4cc(C(N)=O)ccc4o3)CC2)C[C@H]1C(=O)N1CCSC1
null
null
O1CCCC1.O.C(C)N(CC)CC
Acylation
Carboxylic acid to amide conversion
1283aef55d7ee699f097a8e5267689198c76ba671644401547f902657820236d
cb0a71c3fb37a76e96fbd81aae6f95a28398a03d1ad2c8e877085e735efb98f1
O=C([C@@H]1C[C@H](N2CCC(c3nc4ccccc4o3)CC2)CN1)N1CCSC1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]:[c:6]:[#7;a:7].[NH3;D0;+0:8]>>[#7;a:7]:[c:6]:[c:5]:[c:3](-[C;H0;D3;+0:1](-[NH2;D1;+0:8])=[O;D1;H0:2]):[c:4]
null
[]
null
null
30
MINUTE
3-{(2S,4S)-1-tert-Butoxycarbonyl-4-[4-(5-carboxy-2-benzoxazolyl)piperidino]-2-pyrrolidinylcarbonyl}-1,3-thiazolidine [product of Example 310 (1), 1.06 g] was dissolved in tetrahydrofuran (5 mL), and triethylamine (0.279 mL) and isobutyl chlorocarbonate (0.263 mL) were added thereto under ice-cooling. The mixture was st...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid
Primary amide
null
null
C1CC[NH]C1.C1CC[NH]CC1.c1ccc2ocnc2c1.C1CSC[NH]1
HO-
O1CCCC1.O.C(C)N(CC)CC
null
0.5
CC(C)(C)OC(=O)N1C[C@@H](N2CCC(c3nc4cc(C(=O)O)ccc4o3)CC2)C[C@H]1C(=O)N1CCSC1.N>O1CCCC1.O.C(C)N(CC)CC>CC(C)(C)OC(=O)N1C[C@@H](N2CCC(c3nc4cc(C(N)=O)ccc4o3)CC2)C[C@H]1C(=O)N1CCSC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-9aa6435213864e11a89093531e131a22
CC(=O)Cl.CC(C)(C)OC(=O)N1C[C@@H](NCCNc2ccc(C#N)cn2)C[C@H]1C(=O)N1CCSC1>>CC(=O)N(CCNc1ccc(C#N)cn1)[C@H]1C[C@@H](C(=O)N2CCSC2)N(C(=O)OC(C)(C)C)C1
C(O)([O-])=O.[Na+].C(C)(C)(C)OC(=O)N1[C@@H](C[C@@H](C1)NCCNC1=NC=C(C=C1)C#N)C(=O)N1CSCC1.Cl.Cl.Cl.C(#N)C=1C=CC(=NC1)NCCN[C@H]1C[C@H](NC1)C(=O)N1CSCC1.C(C)(=O)Cl>>C(C)(=O)N(CCNC1=NC=C(C=C1)C#N)[C@H]1C[C@H](N(C1)C(=O)OC(C)(C)C)C(=O)N1CSCC1
Cl[C:2]([CH3:1])=[O:3].[NH:4]([CH2:5][CH2:6][NH:7][c:8]1[cH:9][cH:10][c:11]([C:12]#[N:13])[cH:14][n:15]1)[C@H:16]1[CH2:17][C@@H:18]([C:19](=[O:20])[N:21]2[CH2:22][CH2:23][S:24][CH2:25]2)[N:26]([C:27](=[O:28])[O:29][C:30]([CH3:31])([CH3:32])[CH3:33])[CH2:34]1>>[CH3:1][C:2](=[O:3])[N:4]([CH2:5][CH2:6][NH:7][c:8]1[cH:9][c...
CC(=O)Cl.CC(C)(C)OC(=O)N1C[C@@H](NCCNc2ccc(C#N)cn2)C[C@H]1C(=O)N1CCSC1
CC(=O)N(CCNc1ccc(C#N)cn1)[C@H]1C[C@@H](C(=O)N2CCSC2)N(C(=O)OC(C)(C)C)C1
null
null
ClCCl.C(C)N(CC)CC
Acylation
N-alkylation of secondary amines with alkyl halides
b92e0bfd3d683c1f2a209adfe70a67ad7cb0d87749eb59e8fe0cf1689bc291e0
96cb0a2fed10552c5770a45a2d6523b47ac3e38928b4a9c698d8577451182dcd
O=C([C@@H]1C[C@H](NCCNc2ccccn2)CN1)N1CCSC1
Cl-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3].[#7:4]-[C:5]-[C:6](-[NH;D2;+0:7]-[C:8]-[C:9])-[C:10]>>[#7:4]-[C:5]-[C:6](-[N;H0;D3;+0:7](-[C:8]-[C:9])-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3])-[C:10]
null
[]
null
null
5
HOUR
3-{(2S,4S)-1-tert-Butoxycarbonyl-4-{2-[(5-cyano-2-pyridyl)amino]ethyl}amino-2-pyrrolidinylcarbonyl}-1,3-thiazolidine [product of Example 319 (1), 800 mg] and triethylamine (0.42 mL) were dissolved in dichloromethane (20 mL), and acetyl chloride (0.18 mL) was added thereto under ice-cooling. The mixture was stirred at r...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Secondary amine
Tertiary amide
null
null
c1ccncc1.C1CC[NH]C1.C1CSC[NH]1
HCl
ClCCl.C(C)N(CC)CC
null
5
CC(=O)Cl.CC(C)(C)OC(=O)N1C[C@@H](NCCNc2ccc(C#N)cn2)C[C@H]1C(=O)N1CCSC1>ClCCl.C(C)N(CC)CC>CC(=O)N(CCNc1ccc(C#N)cn1)[C@H]1C[C@@H](C(=O)N2CCSC2)N(C(=O)OC(C)(C)C)C1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-61df165efc81456c875f291a49f95b22
C=CC=C.C=Cc1ccccc1>>C=CC=C.C=Cc1ccccc1
CC1=CC=C(C=C)C=C1.C=CC1=CC=CC=C1.C(C)(CC)[Li].C=CC(C)=C.C=CC=C.CC1=CC=C(C=C)C=C1.C=CC1=CC=CC=C1>>C=CC(C)=C.C=CC=C.CC1=CC=C(C=C)C=C1.C=CC1=CC=CC=C1
[CH2:6]=[CH:7][CH:8]=[CH2:9].[CH2:19]=[CH:20][c:21]1[cH:22][cH:23][cH:24][cH:25][cH:26]1>>[CH2:6]=[CH:7][CH:8]=[CH2:9].[CH2:19]=[CH:20][c:21]1[cH:22][cH:23][cH:24][cH:25][cH:26]1
C=CC=C.C=Cc1ccccc1
C=CC=C.C=Cc1ccccc1
null
null
C1CCCCC1
Miscellaneous
OtherReaction
40ba59785861b8226ce5af6bdcbb9a37f0ff50a8c7ec7d4fc4c524cf906cc65c
56ebed4a8b3cebec83c37a71d68f0c87d1e404ab05a9ce792691e4e18a2379dd
c1ccccc1
null
null
[]
null
null
null
null
In a pressure-tight case equipped with a stirrer, 2700 g of cyclohexane, 70 g of a 40:60 monomer mixture of p-methylstyrene and styrene, and 2.52 ml of 1.3 mol cyclohexane solution of sec-butyllithium were placed and polymerized at 50° C. for 120 minutes. The resulting mixture was further polymerized with 326.6 g of a ...
10.6084/m9.figshare.5104873.v1
null
null
null
null
null
c1ccccc1
null
C1CCCCC1
null
null
C=CC=C.C=Cc1ccccc1>C1CCCCC1>C=CC=C.C=Cc1ccccc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-70d5ddae6d1947cb96eb4ce682854070
C=CC=C.C=Cc1ccccc1>>C=CC=C.C=Cc1ccccc1
CC1=CC=C(C=C)C=C1.C=CC1=CC=CC=C1.C(C)(CC)[Li].C=CC(C)=C.C=CC=C.CC1=CC=C(C=C)C=C1.C=CC1=CC=CC=C1>>C=CC(C)=C.C=CC=C.CC1=CC=C(C=C)C=C1.C=CC1=CC=CC=C1
[CH2:6]=[CH:7][CH:8]=[CH2:9].[CH2:19]=[CH:20][c:21]1[cH:22][cH:23][cH:24][cH:25][cH:26]1>>[CH2:6]=[CH:7][CH:8]=[CH2:9].[CH2:19]=[CH:20][c:21]1[cH:22][cH:23][cH:24][cH:25][cH:26]1
C=CC=C.C=Cc1ccccc1
C=CC=C.C=Cc1ccccc1
null
null
C1CCCCC1
Miscellaneous
OtherReaction
40ba59785861b8226ce5af6bdcbb9a37f0ff50a8c7ec7d4fc4c524cf906cc65c
56ebed4a8b3cebec83c37a71d68f0c87d1e404ab05a9ce792691e4e18a2379dd
c1ccccc1
null
null
[]
null
null
null
null
In a pressure-tight case equipped with a stirrer, 2700 g of cyclohexane, 70 g of a 20:80 monomer mixture of p-methylstyrene and styrene, and 2.52 ml of 1.3 mol cyclohexane solution of sec-butyllithium were placed and polymerized at 50° C. for 120 minutes. The resulting mixture was further polymerized with 326.6 g of a ...
10.6084/m9.figshare.5104873.v1
null
null
null
null
null
c1ccccc1
null
C1CCCCC1
null
null
C=CC=C.C=Cc1ccccc1>C1CCCCC1>C=CC=C.C=Cc1ccccc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-a2b5b169b18742f7ae8ae0fa569d6ef7
O=C(O)CCCc1c[nH]c2ccccc12>>O=C(O)CCCc1c[nH]c2ccccc12
C1=CC2=C(C=C1)NC=C2CCCC(=O)O.CC(=C)C(=O)OCCO.C(C1=CC=CC=C1)(=O)OOC(C1=CC=CC=C1)=O>>C1=CC2=C(C=C1)NC=C2CCCC(=O)O.CC(=C)C(=O)OCCO
[O:10]=[C:11]([OH:12])[CH2:13][CH2:14][CH2:15][c:16]1[cH:17][nH:18][c:19]2[cH:20][cH:21][cH:22][cH:23][c:24]12>>[O:10]=[C:11]([OH:12])[CH2:13][CH2:14][CH2:15][c:16]1[cH:17][nH:18][c:19]2[cH:20][cH:21][cH:22][cH:23][c:24]12
O=C(O)CCCc1c[nH]c2ccccc12
O=C(O)CCCc1c[nH]c2ccccc12
null
null
C(C)(=O)OCC
Miscellaneous
OtherReaction
40ba59785861b8226ce5af6bdcbb9a37f0ff50a8c7ec7d4fc4c524cf906cc65c
56ebed4a8b3cebec83c37a71d68f0c87d1e404ab05a9ce792691e4e18a2379dd
c1ccc2[nH]ccc2c1
null
null
[]
60
CELSIUS
null
null
In a glass polymerization bottle were charged 80 g I0A, 18 g IBA, 2 g HEMA, 100 g ethyl acetate, and 0.5 g dibenzoyl peroxide. The bottle was purged with nitrogen, sealed, and tumbled in a water bath maintained at 60° C. for 14 hrs. The resulting terpolymer, IOA/IBA/HEMA, was isolated by precipitation in petroleum ethe...
10.6084/m9.figshare.5104873.v1
null
null
null
null
null
c1ccc2[nH]ccc2c1
null
C(C)(=O)OCC
60
null
O=C(O)CCCc1c[nH]c2ccccc12>C(C)(=O)OCC>O=C(O)CCCc1c[nH]c2ccccc12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-ef7d24618e704333a9b3102d27a16042
C=CC(=O)OCCCCCCCCCCCCCCCCCC>>C=CC(=O)OCCCCCCCCCCCCCCCCCC
C(C=C)(=O)OCCCCCCCCCCCCCCCCCC.CC(=C)C(=O)OCCO.CCC(C)(C#N)N=NC(C)(CC)C#N>>C(C=C)(=O)OCCCCCCCCCCCCCCCCCC.CC(=C)C(=O)OCCO
[CH2:10]=[CH:11][C:12](=[O:13])[O:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32]>>[CH2:10]=[CH:11][C:12](=[O:13])[O:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2...
C=CC(=O)OCCCCCCCCCCCCCCCCCC
C=CC(=O)OCCCCCCCCCCCCCCCCCC
null
null
C(C)(=O)OCC
Miscellaneous
OtherReaction
40ba59785861b8226ce5af6bdcbb9a37f0ff50a8c7ec7d4fc4c524cf906cc65c
56ebed4a8b3cebec83c37a71d68f0c87d1e404ab05a9ce792691e4e18a2379dd
null
null
null
[]
60
CELSIUS
null
null
Crosslinked compositions with low tack can be of use in particular applications. Compositions with these properties are described in the following three examples. In a glass polymerization bottle were charged 72 g IOA, 18 g octadecyl acrylate (ODA), 10 g HEMA, 150 g ethyl acetate, and 0.4 g VAZO-67 (Wako). The bottle w...
10.6084/m9.figshare.5104873.v1
null
null
null
null
null
null
null
C(C)(=O)OCC
60
null
C=CC(=O)OCCCCCCCCCCCCCCCCCC>C(C)(=O)OCC>C=CC(=O)OCCCCCCCCCCCCCCCCCC
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-0cb5f17bb55a4411a16162629ce0c187
O=C1CCc2ccccc21>>C1=Cc2ccccc2C1
C1(CCC2=CC=CC=C12)=O.[BH4-].[Na+].O1CCCC1>>C1C=CC2=CC=CC=C12
O=[C:2]1[CH2:1][CH2:9][c:8]2[c:3]1[cH:4][cH:5][cH:6][cH:7]2>>[CH:1]1=[CH:2][c:3]2[cH:4][cH:5][cH:6][cH:7][c:8]2[CH2:9]1
O=C1CCc2ccccc21
C1=Cc2ccccc2C1
null
null
CO
Miscellaneous
OtherReaction
0be32836af524a7021c2943c6ba4a10e46073e2d9ec6e948809ecba5e7cb2f0e
9db0f73aed071f5fa7238b261fc87a241efa69e871d2f239452605149d0c954e
C1=Cc2ccccc2C1
O=[C;H0;D3;+0:1]1-[CH2;D2;+0:2]-[C:3]-[c:4]:[c:5]-1:[c:6]>>[c:6]:[c:5]1:[c:4]-[C:3]-[CH;D2;+0:2]=[CH;D2;+0:1]-1
null
[]
null
null
null
null
Alternatively, the keto group in the indanone may simply be reduced under standard conditions (e.g. sodium borohydride in methanol and/or tetrahydrofuran (THF)) followed by dehydration to form the desired indene or indene skeleton-containing compound. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Ketone
null
c1ccc2c(c1)CCC2
C1=Cc2ccccc2C1
C1=Cc2ccccc2C1
Other
CO
null
null
O=C1CCc2ccccc21>CO>C1=Cc2ccccc2C1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-c27413ba3f90416cbba4e2a1548bf543
O=C1CCc2c(O)cccc21>>O=C1CCc2ccccc21
O.OC1=C2CCC(C2=CC=C1)=O.N1C=NC=C1.C(C)(C)(C)[Si](Cl)(C)C>>C1CC(=O)C2=CC=CC=C21
O[c:6]1[c:5]2[c:10]([cH:9][cH:8][cH:7]1)[C:2](=[O:1])[CH2:3][CH2:4]2>>[O:1]=[C:2]1[CH2:3][CH2:4][c:5]2[cH:6][cH:7][cH:8][cH:9][c:10]21
O=C1CCc2c(O)cccc21
O=C1CCc2ccccc21
null
null
CN(C)C=O
Reduction
OtherReaction
afd9e864364ae0cef12a16dde11813ff9301e0c6d3277e777bf47b8b23d70231
27ebe27a5e17883303ac9a42d30f2cb918c0044de7ff3c79776e1ddb80cc53d9
O=C1CCc2ccccc21
O-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](:[c:5]-[C:6]=[O;D1;H0:7])-[C:8]>>[C:8]-[c:4](:[c:5]-[C:6]=[O;D1;H0:7]):[cH;D2;+0:1]:[c:2]:[c:3]
79.9
[{"value": 79.9, "product": "C1CC(=O)C2=CC=CC=C21", "details": "PERCENTYIELD", "is_desired": false}, {"value": 79.9, "product": "C1CC(=O)C2=CC=CC=C21", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
To a solution of 4-hydroxy-1-indanone (25.0 g, 169 mmol) and imidazole (28.7 g, 422 mmol) in DMF (500 ml) was added tert-butyldimethylchiorosilane. The reaction mixture was stirred overnight at room temperature and treated with water (500 ml) and extracted with diethyl ether (500 ml). The organic phase was collected an...
10.6084/m9.figshare.5104873.v1
null
Aromatic alcohol
null
c1ccc2c(c1)CCC2
c1ccc2c(c1)CCC2
c1ccc2c(c1)CCC2
Other
CN(C)C=O
null
8
O=C1CCc2c(O)cccc21>CN(C)C=O>O=C1CCc2ccccc21
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-954144c60d7e4434824a463f16a0b3ac
CC(C)(C)[Si](C)(C)Cl.CC1Cc2cccc(O)c2C1=O>>CC1Cc2cccc(O[Si](C)(C)C(C)(C)C)c2C1=O
O.OC=1C=CC=C2CC(C(C12)=O)C.N1C=NC=C1.C(C)(C)(C)[Si](Cl)(C)C>>O([Si](C)(C)C(C)(C)C)C=1C=CC=C2CC(C(C12)=O)C
Cl[Si:10]([CH3:11])([CH3:12])[C:13]([CH3:14])([CH3:15])[CH3:16].[CH3:1][CH:2]1[CH2:3][c:4]2[cH:5][cH:6][cH:7][c:8]([OH:9])[c:17]2[C:18]1=[O:19]>>[CH3:1][CH:2]1[CH2:3][c:4]2[cH:5][cH:6][cH:7][c:8]([O:9][Si:10]([CH3:11])([CH3:12])[C:13]([CH3:14])([CH3:15])[CH3:16])[c:17]2[C:18]1=[O:19]
CC(C)(C)[Si](C)(C)Cl.CC1Cc2cccc(O)c2C1=O
CC1Cc2cccc(O[Si](C)(C)C(C)(C)C)c2C1=O
null
null
CN(C)C=O
Protection
Alcohol protection with silyl ethers
91043baed1393f1ecd2302d7d0b31c01cf171d3977dd7c70afa1da52fa298c73
4a917c959d011f885a1269fa3c1f022ee5e09144996246d24e42e65634a451ac
O=C1CCc2ccccc21
Cl-[Si;H0;D4;+0:1](-[C;D1;H3:2])(-[C;D1;H3:3])-[C:4](-[C;D1;H3:5])(-[C;D1;H3:6])-[C;D1;H3:7].[O;D1;H0:8]=[C:9]-[c:10]:[c:11](-[OH;D1;+0:12]):[c:13]>>[C;D1;H3:2]-[Si;H0;D4;+0:1](-[C;D1;H3:3])(-[O;H0;D2;+0:12]-[c:11](:[c:13]):[c:10]-[C:9]=[O;D1;H0:8])-[C:4](-[C;D1;H3:5])(-[C;D1;H3:6])-[C;D1;H3:7]
null
[]
null
null
8
HOUR
To a solution of 7-hydroxy-2-methyl-1-indanone (6) (10.2 g, 37 mmol) and imidazole (3.02 g, 44 mmol) dissolved in DMF (200 ml) was added tert-butyldimethylchlorosilane (6.11 g, 41 mmol) in DMF (50 ml). The reaction mixture was stirred overnight at room temperature and treated with water (200 ml) and extracted with diet...
10.6084/m9.figshare.5104873.v1
null
Aromatic alcohol.Silyl protective group
TMS ether protective group
null
null
c1ccc2c(c1)CCC2
HCl
CN(C)C=O
null
8
CC(C)(C)[Si](C)(C)Cl.CC1Cc2cccc(O)c2C1=O>CN(C)C=O>CC1Cc2cccc(O[Si](C)(C)C(C)(C)C)c2C1=O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-d3f367f672ce48239ecf93d61c972ddf
CC(C)(C)[Si](C)(C)Cl.O=C1CCc2c(O)cccc21>>CC(C)(C)[Si](C)(C)Oc1cccc2c1CCC2=O
O.OC1=C2CCC(C2=CC=C1)=O.C(C)N(CC)CC.C(C)(C)(C)[Si](Cl)(C)C>>O([Si](C)(C)C(C)(C)C)C1=C2CCC(C2=CC=C1)=O
Cl[Si:5]([C:2]([CH3:1])([CH3:3])[CH3:4])([CH3:6])[CH3:7].[OH:8][c:9]1[cH:10][cH:11][cH:12][c:13]2[c:14]1[CH2:15][CH2:16][C:17]2=[O:18]>>[CH3:1][C:2]([CH3:3])([CH3:4])[Si:5]([CH3:6])([CH3:7])[O:8][c:9]1[cH:10][cH:11][cH:12][c:13]2[c:14]1[CH2:15][CH2:16][C:17]2=[O:18]
CC(C)(C)[Si](C)(C)Cl.O=C1CCc2c(O)cccc21
CC(C)(C)[Si](C)(C)Oc1cccc2c1CCC2=O
null
null
CN(C)C=O
Protection
Alcohol protection with silyl ethers
91043baed1393f1ecd2302d7d0b31c01cf171d3977dd7c70afa1da52fa298c73
4a917c959d011f885a1269fa3c1f022ee5e09144996246d24e42e65634a451ac
O=C1CCc2ccccc21
Cl-[Si;H0;D4;+0:1](-[C;D1;H3:2])(-[C;D1;H3:3])-[C:4](-[C;D1;H3:5])(-[C;D1;H3:6])-[C;D1;H3:7].[OH;D1;+0:8]-[c:9](:[c:10]):[c:11]>>[C;D1;H3:5]-[C:4](-[C;D1;H3:6])(-[C;D1;H3:7])-[Si;H0;D4;+0:1](-[C;D1;H3:2])(-[C;D1;H3:3])-[O;H0;D2;+0:8]-[c:9](:[c:10]):[c:11]
82.8
[{"value": 82.7, "product": "O([Si](C)(C)C(C)(C)C)C1=C2CCC(C2=CC=C1)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 82.8, "product": "O([Si](C)(C)C(C)(C)C)C1=C2CCC(C2=CC=C1)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
To a solution of 4-hydroxy-1-indanone (25.0 g, 169 mmol) in DMF (500 ml) was triethylamine (22.2 g, 220 mmol) added, to the resulting solution was tert-butyldimethylchlorosilane (28.0 g, 186 mmol) added. The reaction mixture was stirred overnight at room temperature and treated with water (500 ml) and extracted with di...
10.6084/m9.figshare.5104873.v1
null
Aromatic alcohol.Silyl protective group
TMS ether protective group
null
null
c1ccc2c(c1)CCC2
HCl
CN(C)C=O
null
8
CC(C)(C)[Si](C)(C)Cl.O=C1CCc2c(O)cccc21>CN(C)C=O>CC(C)(C)[Si](C)(C)Oc1cccc2c1CCC2=O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-2eff2f10331b4e68bad3123965ac0956
CC(C)(C)[Si](C)(C)Oc1cccc2c1CCC2=O>>Oc1cccc2c1C=CC2
O([Si](C)(C)C(C)(C)C)C1=C2CCC(C2=CC=C1)=O.[F-].C(CCC)[N+](CCCC)(CCCC)CCCC.Cl.C(C(=O)O)(=O)O.[NH4+].[Cl-].[BH4-].[Na+]>>OC1=C2C=CCC2=CC=C1
CC(C)(C)[Si](C)(C)[O:1][c:2]1[cH:3][cH:4][cH:5][c:6]2[c:7]1[CH2:8][CH2:9][C:10]2=O>>[OH:1][c:2]1[cH:3][cH:4][cH:5][c:6]2[c:7]1[CH:8]=[CH:9][CH2:10]2
CC(C)(C)[Si](C)(C)Oc1cccc2c1CCC2=O
Oc1cccc2c1C=CC2
null
null
CO.C1CCOC1
Functional Group Interconversion
OtherReaction
be130c8a5e55734cd2b2af0b79058d40d1fec3efc3bf58d687e6527259482781
46a40dcb0b03cb539403c87f5504d123d46819138b107daa53759e3da1668131
C1=Cc2ccccc2C1
C-C(-C)(-C)-[Si](-C)(-C)-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]1:[c:5](:[c:6])-[C;H0;D3;+0:7](=O)-[CH2;D2;+0:8]-[CH2;D2;+0:9]-1>>[OH;D1;+0:1]-[c:2](:[c:3]):[c:4]1:[c:5](:[c:6])-[CH2;D2;+0:7]-[CH;D2;+0:8]=[CH;D2;+0:9]-1
65.1
[{"value": 65.1, "product": "OC1=C2C=CCC2=CC=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 65.1, "product": "OC1=C2C=CCC2=CC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
To a solution of 4-(tert-butyldimethylsiloxy)-1-indanone (35.0 g, 133 mmol) in methanol/THF (100 ml:200 ml) was NaBH4 (7.57 g, 200 mmol) added in portions at 0° C. The reaction mixture is stirred overnight. The resulting solution is poured on ice, acidified with concentrated hydrochloric acid to pH=1 and extracted with...
10.6084/m9.figshare.5104873.v1
null
Ketone.TMS ether protective group
Aromatic alcohol
c1ccc2c(c1)CCC2
C1=Cc2ccccc2C1
C1=Cc2ccccc2C1
HO-
CO.C1CCOC1
null
8
CC(C)(C)[Si](C)(C)Oc1cccc2c1CCC2=O>CO.C1CCOC1>Oc1cccc2c1C=CC2
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-eda8294c306d46c180abf6eac9bf154e
CCN1CC=CB1c1ccccc1>>CCN1C=C[CH-]B1c1ccccc1
C(C)N1B(C=CC1)C1=CC=CC=C1.C(C)(C)[N-]C(C)C.[Li+]>>C(C)N1B([CH-]C=C1)C1=CC=CC=C1.[Li+]
[CH3:1][CH2:2][N:3]1[CH2:4][CH:5]=[CH:6][B:7]1[c:8]1[cH:9][cH:10][cH:11][cH:12][cH:13]1>>[CH3:1][CH2:2][N:3]1[CH:4]=[CH:5][CH-:6][B:7]1[c:8]1[cH:9][cH:10][cH:11][cH:12][cH:13]1
CCN1CC=CB1c1ccccc1
CCN1C=C[CH-]B1c1ccccc1
null
null
CCOCC
Functional Group Addition
OtherReaction
d558737e1105e7bd7b5be3615d72379bceb9091db9732de9d593410fdadd3e04
fc933fdd7baf3b8acf9bd94a15b8568b76358dfcf07000fc6c83b12a47ed99ee
C1=CNB(c2ccccc2)[CH-]1
[C:1]-[#7:2]1-[CH2;D2;+0:3]-[CH;D2;+0:4]=[CH;D2;+0:5]-[#5:6]-1-[c:7]>>[C:1]-[#7:2]1-[CH;D2;+0:3]=[CH;D2;+0:4]-[CH-;D2:5]-[#5:6]-1-[c:7]
77
[{"value": 77.0, "product": "C(C)N1B([CH-]C=C1)C1=CC=CC=C1.[Li+]", "details": "PERCENTYIELD", "is_desired": false}, {"value": 75.5, "product": "C(C)N1B([CH-]C=C1)C1=CC=CC=C1.[Li+]", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
25
CELSIUS
10
HOUR
1,5-Dihydro-1-ethyl-2-phenyl-1,2-azaborole (5.0 g, 29.2 mmol) was dissolved in 15 mL of ether at −78° C. To this was added a solution of lithiumdiisopropylamide (3.13 g, 29.2 mmol) in 15 mL of ether. The mixture was stirred at −78° C. for 2 hours and at 25° C. for 10 hours. After removal of the solvent the residue was ...
10.6084/m9.figshare.5104873.v1
null
null
Enamine
[B]1C=CC[NH]1
[B]1[CH-]C=C[NH]1
[B]1[CH-]C=C[NH]1.c1ccccc1
null
CCOCC
25
10
CCN1CC=CB1c1ccccc1>CCOCC>CCN1C=C[CH-]B1c1ccccc1