dataset_id
large_stringclasses
414 values
reaction_id
large_stringlengths
36
36
reaction_smiles
large_stringlengths
4
873
rxn_insight_reaction
large_stringlengths
19
1.07k
mapped_reaction_smiles
large_stringlengths
14
3.37k
reactant_smiles
large_stringlengths
1
581
product_smiles
large_stringlengths
1
433
reagent_smiles
large_stringclasses
634 values
catalyst_smiles
large_stringlengths
1
683
solvent_smiles
large_stringlengths
1
245
rxn_insight_class
large_stringclasses
11 values
rxn_insight_name
large_stringclasses
346 values
rxn_insight_tag
large_stringlengths
64
64
rxn_insight_tag2
large_stringlengths
64
64
rxn_insight_scaffold
large_stringlengths
5
288
rxn_insight_template
large_stringlengths
24
2.64k
yield_percent
float64
-0.8
90,205,160,000B
yield_measurements
large_stringlengths
2
864
temperature_value
float64
-230
30.1k
temperature_units
large_stringclasses
3 values
reaction_time_value
float64
0
4k
time_units
large_stringclasses
4 values
procedure_details
large_stringlengths
1
23.6k
reference
large_stringclasses
96 values
doi
large_stringclasses
19 values
functional_groups_reactants
large_stringlengths
3
716
functional_groups_products
large_stringlengths
3
539
participating_rings_reactants
large_stringlengths
5
293
participating_rings_products
large_stringlengths
5
271
all_rings_products
large_stringlengths
5
271
byproduct_smiles
large_stringclasses
176 values
agent_smiles
large_stringlengths
1
712
temperature_c
float64
-230
30.1k
reaction_time_hours
float64
0
2.16k
reaction_smiles_with_agents
large_stringlengths
4
882
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-517acf81c55344f99fba65175862b982
ClCCCBr.Cn1c(C(O)c2ccc(Cl)cc2)cnc1S>>Cn1c(C(O)c2ccc(Cl)cc2)cnc1SCCCCl
ClC1=CC=C(C=C1)C(O)C=1N(C(=NC1)S)C.C(=O)([O-])[O-].[K+].[K+].BrCCCCl>>ClC1=CC=C(C=C1)C(O)C=1N(C(=NC1)SCCCCl)C
Br[CH2:17][CH2:18][CH2:19][Cl:20].[CH3:1][n:2]1[c:3]([CH:4]([OH:5])[c:6]2[cH:7][cH:8][c:9]([Cl:10])[cH:11][cH:12]2)[cH:13][n:14][c:15]1[SH:16]>>[CH3:1][n:2]1[c:3]([CH:4]([OH:5])[c:6]2[cH:7][cH:8][c:9]([Cl:10])[cH:11][cH:12]2)[cH:13][n:14][c:15]1[S:16][CH2:17][CH2:18][CH2:19][Cl:20]
ClCCCBr.Cn1c(C(O)c2ccc(Cl)cc2)cnc1S
Cn1c(C(O)c2ccc(Cl)cc2)cnc1SCCCCl
null
null
CC(=O)C.CN(C)C=O
Heteroatom Alkylation and Arylation
thioether_nucl_sub
26df88c6a3f5f203c89584658be4e126cb42994c98a2e16bc812e1036cdae857
8b2f52296c3a93039174c980b6042ba15754e04d6892a1284c3a32985220b214
c1ccc(Cc2cnc[nH]2)cc1
Br-[CH2;D2;+0:1]-[C:2]-[C:3].[C;D1;H3:4]-[#7;a:5]1:[c:6]:[c:7]:[#7;a:8]:[c:9]:1-[SH;D1;+0:10]>>[C:3]-[C:2]-[CH2;D2;+0:1]-[S;H0;D2;+0:10]-[c:9]1:[#7;a:8]:[c:7]:[c:6]:[#7;a:5]:1-[C;D1;H3:4]
69
[{"value": 69.0, "product": "ClC1=CC=C(C=C1)C(O)C=1N(C(=NC1)SCCCCl)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 68.4, "product": "ClC1=CC=C(C=C1)C(O)C=1N(C(=NC1)SCCCCl)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
16
HOUR
The product of Example I, Step A (0.09 g) in acetone (2 mL) and DMF (2 mL) was treated with K2CO3 (0.2 g) followed by 1-bromo-3-chloropropane (0.11 g). The mixture was allowed to stir at rt for 16 h and was then partitioned between EtOAc (50 mL) and brine (50 mL). The organic layer was separated and washed with brine (...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic thiol
Monosulfide
null
null
c1cnc[nH]1.c1ccccc1
HBr
CC(=O)C.CN(C)C=O
null
16
ClCCCBr.Cn1c(C(O)c2ccc(Cl)cc2)cnc1S>CC(=O)C.CN(C)C=O>Cn1c(C(O)c2ccc(Cl)cc2)cnc1SCCCCl
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-11ad7b5b2b0443ce966e181291007d7a
Cn1c(C(=O)c2ccc(Br)cc2)cnc1SCCCN1CCCCC1>>Cn1c(C(O)c2ccc(Br)cc2)cnc1SCCCN1CCCCC1
BrC1=CC=C(C=C1)C(=O)C=1N(C(=NC1)SCCCN1CCCCC1)C>>BrC1=CC=C(C=C1)C(O)C=1N(C(=NC1)SCCCN1CCCCC1)C
[CH3:1][n:2]1[c:3]([C:4](=[O:5])[c:6]2[cH:7][cH:8][c:9]([Br:10])[cH:11][cH:12]2)[cH:13][n:14][c:15]1[S:16][CH2:17][CH2:18][CH2:19][N:20]1[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]1>>[CH3:1][n:2]1[c:3]([CH:4]([OH:5])[c:6]2[cH:7][cH:8][c:9]([Br:10])[cH:11][cH:12]2)[cH:13][n:14][c:15]1[S:16][CH2:17][CH2:18][CH2:19][N:20]1[C...
Cn1c(C(=O)c2ccc(Br)cc2)cnc1SCCCN1CCCCC1
Cn1c(C(O)c2ccc(Br)cc2)cnc1SCCCN1CCCCC1
null
O=[Mn]=O
null
Reduction
Reduction of ketone to secondary alcohol
02790ac194d8bf7ccb13d6247c59412024d87f77d2c906ef7804f021f57d5070
1bd3cd74b454139c0a0068ac0135836499926b274bff569df163210c6c944a89
c1ccc(Cc2cnc(SCCCN3CCCCC3)[nH]2)cc1
[C;D1;H3:1]-[#7;a:2]1:[c:3]:[#7;a:4]:[c:5]:[c:6]:1-[C;H0;D3;+0:7](=[O;H0;D1;+0:8])-[c:9](:[c:10]):[c:11]>>[C;D1;H3:1]-[#7;a:2]1:[c:3]:[#7;a:4]:[c:5]:[c:6]:1-[CH;D3;+0:7](-[OH;D1;+0:8])-[c:9](:[c:10]):[c:11]
20
[{"value": 20.0, "product": "BrC1=CC=C(C=C1)C(O)C=1N(C(=NC1)SCCCN1CCCCC1)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The product of Example III, Step B (0.11 g) in acetone (5 mL) and DMF (5 mL) was treated with piperidine (0.22 g) and K2CO3 (1.8 g). The reaction mixture was allowed to stir for 16 h and then partitioned between EtOAc (75 mL) and aqueous (aq.) saturated (satd.) NaHCO3 (50 mL). The organic portion was washed with brine ...
10.6084/m9.figshare.5104873.v1
null
Ketone
Secondary alcohol
null
null
c1cnc[nH]1.c1ccccc1.C1CC[NH]CC1
null
O=[Mn]=O
null
null
Cn1c(C(=O)c2ccc(Br)cc2)cnc1SCCCN1CCCCC1>O=[Mn]=O>Cn1c(C(O)c2ccc(Br)cc2)cnc1SCCCN1CCCCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-7cf15beb6df540968fa3d3aaa5a6be29
CCCBr.Cn1c(C(O)c2ccc(Cl)cc2)cnc1S>>CCCSc1ncc(C(O)c2ccc(Cl)cc2)n1C
ClC1=CC=C(C=C1)C(O)C=1N(C(=NC1)S)C.BrCCC>>ClC1=CC=C(C=C1)C(O)C=1N(C(=NC1)SCCC)C
Br[CH2:3][CH2:2][CH3:1].[SH:4][c:5]1[n:6][cH:7][c:8]([CH:9]([OH:10])[c:11]2[cH:12][cH:13][c:14]([Cl:15])[cH:16][cH:17]2)[n:18]1[CH3:19]>>[CH3:1][CH2:2][CH2:3][S:4][c:5]1[n:6][cH:7][c:8]([CH:9]([OH:10])[c:11]2[cH:12][cH:13][c:14]([Cl:15])[cH:16][cH:17]2)[n:18]1[CH3:19]
CCCBr.Cn1c(C(O)c2ccc(Cl)cc2)cnc1S
CCCSc1ncc(C(O)c2ccc(Cl)cc2)n1C
null
null
null
Heteroatom Alkylation and Arylation
thioether_nucl_sub
26df88c6a3f5f203c89584658be4e126cb42994c98a2e16bc812e1036cdae857
8b2f52296c3a93039174c980b6042ba15754e04d6892a1284c3a32985220b214
c1ccc(Cc2cnc[nH]2)cc1
Br-[CH2;D2;+0:1]-[C:2]-[C;D1;H3:3].[C;D1;H3:4]-[#7;a:5]1:[c:6]:[c:7]:[#7;a:8]:[c:9]:1-[SH;D1;+0:10]>>[C;D1;H3:4]-[#7;a:5]1:[c:6]:[c:7]:[#7;a:8]:[c:9]:1-[S;H0;D2;+0:10]-[CH2;D2;+0:1]-[C:2]-[C;D1;H3:3]
71
[{"value": 71.0, "product": "ClC1=CC=C(C=C1)C(O)C=1N(C(=NC1)SCCC)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The product of Example I, Step A (3.35 g) was subjected to the same conditions as described in Example I, Step B except that bromopropane (1.4 mL) was employed as the alkylating agent to provide (4-Chlorophenyl)-(3-methyl-2-propylsulfanyl-3H-imidazol-4-yl)-methanol (2.69 g, 71%). M calc=296; M+H found=297. Calculated f...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic thiol
Monosulfide
null
null
c1c[nH]cn1.c1ccccc1
HBr
null
null
null
CCCBr.Cn1c(C(O)c2ccc(Cl)cc2)cnc1S>>CCCSc1ncc(C(O)c2ccc(Cl)cc2)n1C
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a571ddaab69d4c9f82dbb29e0efdbdb4
CN(C)CCCSc1ncc(C(=O)c2ccc(Cl)cc2)n1C.OO>>CN(C)CCCS(=O)c1ncc(C(=O)c2ccc(Cl)cc2)n1C
[OH-].[Na+].O.ClC1=CC=C(C=C1)C(=O)C=1N(C(=NC1)SCCCN(C)C)C.OO>>ClC1=CC=C(C=C1)C(=O)C=1N(C(=NC1)S(=O)CCCN(C)C)C
[CH3:1][N:2]([CH3:3])[CH2:4][CH2:5][CH2:6][S:7][c:9]1[n:10][cH:11][c:12]([C:13](=[O:14])[c:15]2[cH:16][cH:17][c:18]([Cl:19])[cH:20][cH:21]2)[n:22]1[CH3:23].O[OH:8]>>[CH3:1][N:2]([CH3:3])[CH2:4][CH2:5][CH2:6][S:7](=[O:8])[c:9]1[n:10][cH:11][c:12]([C:13](=[O:14])[c:15]2[cH:16][cH:17][c:18]([Cl:19])[cH:20][cH:21]2)[n:22]1...
CN(C)CCCSc1ncc(C(=O)c2ccc(Cl)cc2)n1C.OO
CN(C)CCCS(=O)c1ncc(C(=O)c2ccc(Cl)cc2)n1C
null
null
C(C)(=O)O
Oxidation
Sulfanyl to sulfinyl_H2O2
3f94fa67dce0f9d1622f25c2f6b679e0a2528e6d5c5559b15aed37456745a4b5
099322fb111e24ec324e6fad75d493a762ca0cd5af0df8c6f3bfd25c910b45a8
O=C(c1ccccc1)c1cnc[nH]1
O-[OH;D1;+0:1].[C:2]-[C:3]-[S;H0;D2;+0:4]-[c:5]1:[#7;a:6]:[c:7]:[c:8](-[C:9]=[O;D1;H0:10]):[#7;a:11]:1-[C;D1;H3:12]>>[C:2]-[C:3]-[S;H0;D3;+0:4](=[O;H0;D1;+0:1])-[c:5]1:[#7;a:6]:[c:7]:[c:8](-[C:9]=[O;D1;H0:10]):[#7;a:11]:1-[C;D1;H3:12]
null
[]
null
null
48
HOUR
To a stirred solution of (4-Chloro-phenyl)-[2-(3-dimethylamino-propylsulfanyl)-3-methyl-3H-imidazol-4-yl]-methanone (135 mg) in glacial acetic acid (4.00 mL) was added at rt H2O2 (82.0 μL; 30 wt. % in water). The reaction solution was stirred for 48 h at rt, and water (10.0 mL) was added. The solution was brought to pH...
10.6084/m9.figshare.5104873.v1
null
Peroxide.Monosulfide
Sulfoxide
null
null
c1c[nH]cn1.c1ccccc1
HO-
C(C)(=O)O
null
48
CN(C)CCCSc1ncc(C(=O)c2ccc(Cl)cc2)n1C.OO>C(C)(=O)O>CN(C)CCCS(=O)c1ncc(C(=O)c2ccc(Cl)cc2)n1C
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-30840878b9f5488a905dae2b4792dd68
CNOC.O=C(Cl)c1ccc(Cl)cc1>>CON(C)C(=O)c1ccc(Cl)cc1
ClC1=CC=C(C(=O)Cl)C=C1.Cl.CNOC.C(C)N(CC)CC>>ClC1=CC=C(C(=O)N(C)OC)C=C1
[CH3:1][O:2][NH:3][CH3:4].Cl[C:5](=[O:6])[c:7]1[cH:8][cH:9][c:10]([Cl:11])[cH:12][cH:13]1>>[CH3:1][O:2][N:3]([CH3:4])[C:5](=[O:6])[c:7]1[cH:8][cH:9][c:10]([Cl:11])[cH:12][cH:13]1
CNOC.O=C(Cl)c1ccc(Cl)cc1
CON(C)C(=O)c1ccc(Cl)cc1
null
null
C(Cl)Cl
Acylation
N-alkylation of secondary amines with alkyl halides
b92e0bfd3d683c1f2a209adfe70a67ad7cb0d87749eb59e8fe0cf1689bc291e0
96cb0a2fed10552c5770a45a2d6523b47ac3e38928b4a9c698d8577451182dcd
c1ccccc1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C;D1;H3:6]-[#8:7]-[NH;D2;+0:8]-[C;D1;H3:9]>>[C;D1;H3:6]-[#8:7]-[N;H0;D3;+0:8](-[C;D1;H3:9])-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
92.7
[{"value": 92.0, "product": "ClC1=CC=C(C(=O)N(C)OC)C=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 92.7, "product": "ClC1=CC=C(C(=O)N(C)OC)C=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
8
HOUR
A 1-L, three-necked, round-bottomed flask equipped with a magnetic stirrer, nitrogen inlet and an addition funnel was charged with N,O-dimethylhydroxylamine hydrochloride (20 g, 0.20 mol) and CH2Cl2 (250 mL). The mixture was cooled to 0° C. and triethylamine (24 g, 0.20 mol) was added, followed by a solution of 4-chlor...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Secondary amine
Tertiary amide
null
null
c1ccccc1
HCl
C(Cl)Cl
0
8
CNOC.O=C(Cl)c1ccc(Cl)cc1>C(Cl)Cl>CON(C)C(=O)c1ccc(Cl)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-33784d9269ba4120a88d59e8cd38a9a7
CC(C)N1CCC(CO)CC1.Cn1c(C(=O)c2ccc(Cl)cc2)cnc1Cl>>CC(C)N1CCC(COc2ncc(C(=O)c3ccc(Cl)cc3)n2C)CC1
ClC1=NC=C(N1C)C(=O)C1=CC=C(C=C1)Cl.[H-].[Na+].C(C)(C)N1CCC(CC1)CO>>ClC1=CC=C(C=C1)C(=O)C=1N(C(=NC1)OCC1CCN(CC1)C(C)C)C
[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([CH2:8][OH:9])[CH2:25][CH2:26]1.Cl[c:10]1[n:11][cH:12][c:13]([C:14](=[O:15])[c:16]2[cH:17][cH:18][c:19]([Cl:20])[cH:21][cH:22]2)[n:23]1[CH3:24]>>[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([CH2:8][O:9][c:10]2[n:11][cH:12][c:13]([C:14](=[O:15])[c:16]3[cH:17][cH:18][c...
CC(C)N1CCC(CO)CC1.Cn1c(C(=O)c2ccc(Cl)cc2)cnc1Cl
CC(C)N1CCC(COc2ncc(C(=O)c3ccc(Cl)cc3)n2C)CC1
null
null
C1CCOC1
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
dd7acae407244f874fe9cfeba5336cc9dccd653601cdd03778244273ecfb33d8
a4cafa7bcd156e21cca6eaac1b32e28ec8540642a31181122e6957f3d7559631
O=C(c1ccccc1)c1cnc(OCC2CCNCC2)[nH]1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[c:4](-[C:5]=[O;D1;H0:6]):[#7;a:7]:1-[C;D1;H3:8].[C:9]-[C:10]-[OH;D1;+0:11]>>[C:9]-[C:10]-[O;H0;D2;+0:11]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[c:4](-[C:5]=[O;D1;H0:6]):[#7;a:7]:1-[C;D1;H3:8]
78
[{"value": 78.0, "product": "ClC1=CC=C(C=C1)C(=O)C=1N(C(=NC1)OCC1CCN(CC1)C(C)C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 77.6, "product": "ClC1=CC=C(C=C1)C(=O)C=1N(C(=NC1)OCC1CCN(CC1)C(C)C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
2
HOUR
To a 1-L, three-necked, round-bottomed flask equipped with a magnetic stirrer, nitrogen inlet and an addition funnel was added NaH (1.45 g, 0.061 mol) and THF (300 mL). The stirred suspension was cooled to 0° C. and (1-isopropyl-piperidin-4-yl)-methanol (9.5 g, 0.06 mol) was added. The cooling bath was removed, and the...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary alcohol
Ether
c1c[nH]cn1
c1c[nH]cn1
C1CC[NH]CC1.c1c[nH]cn1.c1ccccc1
HCl
C1CCOC1
0
2
CC(C)N1CCC(CO)CC1.Cn1c(C(=O)c2ccc(Cl)cc2)cnc1Cl>C1CCOC1>CC(C)N1CCC(COc2ncc(C(=O)c3ccc(Cl)cc3)n2C)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-162b6e4d486440c3b824c1d7e9705d69
CN1CCC(Sc2ncc(C(O[Si](C)(C)C(C)(C)C)c3cccc(F)c3)n2C)CC1>>CN1CCC(Sc2ncc(C(O)c3cccc(F)c3)n2C)CC1
FC=1C=C(C=CC1)C(C1=CN=C(N1C)SC1CCN(CC1)C)O[Si](C)(C)C(C)(C)C.[H-].[Na+].FC=1C=C(C=CC1)C(C1=CN=C(N1C)Cl)O[Si](C)(C)C(C)(C)C>>FC=1C=C(C=CC1)C(O)C=1N(C(=NC1)SC1CCN(CC1)C)C
CC(C)(C)[Si](C)(C)[O:12][CH:11]([c:10]1[cH:9][n:8][c:7]([S:6][CH:5]2[CH2:4][CH2:3][N:2]([CH3:1])[CH2:23][CH2:22]2)[n:20]1[CH3:21])[c:13]1[cH:14][cH:15][cH:16][c:17]([F:18])[cH:19]1>>[CH3:1][N:2]1[CH2:3][CH2:4][CH:5]([S:6][c:7]2[n:8][cH:9][c:10]([CH:11]([OH:12])[c:13]3[cH:14][cH:15][cH:16][c:17]([F:18])[cH:19]3)[n:20]2[...
CN1CCC(Sc2ncc(C(O[Si](C)(C)C(C)(C)C)c3cccc(F)c3)n2C)CC1
CN1CCC(Sc2ncc(C(O)c3cccc(F)c3)n2C)CC1
null
null
C1CCOC1
Deprotection
Alcohol deprotection from silyl ethers
050b4fb4e1e9936189860d27dded10ae70a294a642c52f800eb9d5aaef7955cc
88623e19d23cdfe8e1a4c167fd6cfc51d774a1c784b87a7bb2df8153ee93e67a
c1ccc(Cc2cnc(SC3CCNCC3)[nH]2)cc1
C-C(-C)(-C)-[Si](-C)(-C)-[O;H0;D2;+0:1]-[C:2](-[c:3])-[c:4](:[#7;a:5]):[c:6]:[#7;a:7]>>[#7;a:5]:[c:4](-[C:2](-[OH;D1;+0:1])-[c:3]):[c:6]:[#7;a:7]
null
[]
null
null
30
MINUTE
4-{5-[(3-Fluoro-phenyl)-(tert-butyl-dimethyl-silanyloxy)-methyl]-1-methyl-1H-imidazol-2-ylsulfanyl}-1-methyl-piperidine. To a 0° C. solution of 1-methyl-piperidine-thiol (1.5 equivalents) in THF (0.2 M) is added NaH (60% dispersion in oil, 1.5 equivalents). After 30 min, 5-[(3-fluoro-phenyl)-(tert-butyl-dimethyl-silany...
10.6084/m9.figshare.5104873.v1
null
TMS ether protective group
Secondary alcohol
null
null
C1CC[NH]CC1.c1c[nH]cn1.c1ccccc1
Other
C1CCOC1
null
0.5
CN1CCC(Sc2ncc(C(O[Si](C)(C)C(C)(C)C)c3cccc(F)c3)n2C)CC1>C1CCOC1>CN1CCC(Sc2ncc(C(O)c3cccc(F)c3)n2C)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-1e436c8e703f4c7799339d289b3f6850
CC(C)N1CCC(Oc2cc3cc(C(=O)O)[nH]c3cc2Br)CC1.O=S(=O)(N1CCCCC1)N1CCNCC1>>CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)N5CCCCC5)CC4)[nH]c3cc2Br)CC1
Cl.BrC1=C(C=C2C=C(NC2=C1)C(=O)O)OC1CCN(CC1)C(C)C.F[B-](F)(F)F.N1(N=NC2=C1C=CC=C2)OC(=[N+](C)C)N(C)C.N1(CCCCC1)S(=O)(=O)N1CCNCC1.C(C)(C)N(C(C)C)CC.C([O-])(O)=O.[Na+]>>BrC1=C(C=C2C=C(NC2=C1)C(=O)N1CCN(CC1)S(=O)(=O)N1CCCCC1)OC1CCN(CC1)C(C)C
O[C:14]([c:13]1[cH:12][c:11]2[cH:10][c:9]([O:8][CH:7]3[CH2:6][CH2:5][N:4]([CH:2]([CH3:1])[CH3:3])[CH2:37][CH2:36]3)[c:34]([Br:35])[cH:33][c:32]2[nH:31]1)=[O:15].[NH:16]1[CH2:17][CH2:18][N:19]([S:20](=[O:21])(=[O:22])[N:23]2[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]2)[CH2:29][CH2:30]1>>[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][...
CC(C)N1CCC(Oc2cc3cc(C(=O)O)[nH]c3cc2Br)CC1.O=S(=O)(N1CCCCC1)N1CCNCC1
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)N5CCCCC5)CC4)[nH]c3cc2Br)CC1
null
null
CN(C=O)C
Acylation
Acylation of Nitrogen Nucleophiles by Carboxylic Acids
ed26ef5eea92a0cc433b3f89a34f4c61724425fa15a9d0ec83a0f7a903eec831
c5e4172490b2731ba9322b68af56376edadc31ce0bb9a3dfdea23a1817a852fd
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCN(S(=O)(=O)N2CCCCC2)CC1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#7;a:5]:[c:6].[#7:7]1-[C:8]-[C:9]-[NH;D2;+0:10]-[C:11]-[C:12]-1>>[O;D1;H0:2]=[C;H0;D3;+0:1](-[N;H0;D3;+0:10]1-[C:9]-[C:8]-[#7:7]-[C:12]-[C:11]-1)-[c:3](:[c:4]):[#7;a:5]:[c:6]
56
[{"value": 56.0, "product": "BrC1=C(C=C2C=C(NC2=C1)C(=O)N1CCN(CC1)S(=O)(=O)N1CCCCC1)OC1CCN(CC1)C(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 55.9, "product": "BrC1=C(C=C2C=C(NC2=C1)C(=O)N1CCN(CC1)S(=O)(=O)N1CCCCC1)OC1CCN(CC1)C(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
To a solution of 0.5 g (1.20 mmol) 6-bromo-5-(1-isopropyl-piperidin-4-yloxy)-1H-indole-2-carboxylic acid hydrochloride in 8 mL N,N-dimethylformamide, 0.48 g (1.50 mmol) O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate, 0.31 g (1.33 mmol) 1-(piperidin-1-yl-sulfonyl)-piperazine and 1.0 mL (0.77 g, 6.0...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Secondary amine
Tertiary amide
C1CNCC[NH]1
C1C[NH]CC[NH]1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1.C1CC[NH]CC1
HO-
CN(C=O)C
null
null
CC(C)N1CCC(Oc2cc3cc(C(=O)O)[nH]c3cc2Br)CC1.O=S(=O)(N1CCCCC1)N1CCNCC1>CN(C=O)C>CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)N5CCCCC5)CC4)[nH]c3cc2Br)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-4b5d9e30fc7b4282b9a64386311c57ff
CC(C)N1CCC(O)CC1.CCOC(=O)c1cc2cc(O)c(Br)cc2[nH]1>>CCOC(=O)c1cc2cc(OC3CCN(C(C)C)CC3)c(Br)cc2[nH]1
N(=NC(=O)OC(C)(C)C)C(=O)OC(C)(C)C.C(C)OC(=O)C=1NC2=CC(=C(C=C2C1)O)Br.C(C)(C)N1CCC(CC1)O.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1>>C(C)OC(=O)C=1NC2=CC(=C(C=C2C1)OC1CCN(CC1)C(C)C)Br
O[CH:12]1[CH2:13][CH2:14][N:15]([CH:16]([CH3:17])[CH3:18])[CH2:19][CH2:20]1.[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]2[cH:9][c:10]([OH:11])[c:21]([Br:22])[cH:23][c:24]2[nH:25]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]2[cH:9][c:10]([O:11][CH:12]3[CH2:13][CH2:14][N:15]([CH:16]([CH3:17])[CH3:18])[CH2:19]...
CC(C)N1CCC(O)CC1.CCOC(=O)c1cc2cc(O)c(Br)cc2[nH]1
CCOC(=O)c1cc2cc(OC3CCN(C(C)C)CC3)c(Br)cc2[nH]1
null
null
O1CCCC1
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
a9e936b0e9135225700edbab1c7696738b7f1f0756494b6ceeeda63b184d572f
776ba735002e33225fbc578943016110c2c43efefd97bfeea4ec3cc2e2e1532f
c1cc2cc(OC3CCNCC3)ccc2[nH]1
O-[CH;D3;+0:1]1-[C:2]-[C:3]-[#7:4]-[C:5]-[C:6]-1.[OH;D1;+0:7]-[c:8](:[c:9]):[c:10]>>[c:9]:[c:8](-[O;H0;D2;+0:7]-[CH;D3;+0:1]1-[C:2]-[C:3]-[#7:4]-[C:5]-[C:6]-1):[c:10]
76
[{"value": 76.0, "product": "C(C)OC(=O)C=1NC2=CC(=C(C=C2C1)OC1CCN(CC1)C(C)C)Br", "details": "PERCENTYIELD", "is_desired": false}, {"value": 75.7, "product": "C(C)OC(=O)C=1NC2=CC(=C(C=C2C1)OC1CCN(CC1)C(C)C)Br", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
18
HOUR
To a suspension of 5.7 g (20.0 mmol) 6-bromo-5-hydroxy-1H-indole-2-carboxylic acid ethyl ester in 120 mL tetrahydrofuran, 3.44 g (24.0 mmol) isopropyl-piperidin-4-ol and 6.30 g (24.0 mmol) triphenylphosphine were added. The suspension was cooled to 0° C. and 5.53 g (24.0 mmol) di-tert-butyl azodicarboxylate was added. ...
10.6084/m9.figshare.5104873.v1
null
Secondary alcohol.Aromatic alcohol
Ether
C1CC[NH]CC1
C1CC[NH]CC1
c1ccc2[nH]ccc2c1.C1CC[NH]CC1
HO-
O1CCCC1
0
18
CC(C)N1CCC(O)CC1.CCOC(=O)c1cc2cc(O)c(Br)cc2[nH]1>O1CCCC1>CCOC(=O)c1cc2cc(OC3CCN(C(C)C)CC3)c(Br)cc2[nH]1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-4dd177b61f4645da8471e1b54c07186b
CCOC(=O)c1cc2cc(OC)c(Br)cc2[nH]1>>CCOC(=O)c1cc2cc(O)c(Br)cc2[nH]1
C(C)OC(=O)C=1NC2=CC(=C(C=C2C1)OC)Br.B(Br)(Br)Br.C([O-])(O)=O.[Na+]>>C(C)OC(=O)C=1NC2=CC(=C(C=C2C1)O)Br
C[O:11][c:10]1[cH:9][c:8]2[cH:7][c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[nH:16][c:15]2[cH:14][c:12]1[Br:13]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]2[cH:9][c:10]([OH:11])[c:12]([Br:13])[cH:14][c:15]2[nH:16]1
CCOC(=O)c1cc2cc(OC)c(Br)cc2[nH]1
CCOC(=O)c1cc2cc(O)c(Br)cc2[nH]1
null
null
ClCCl
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc2[nH]ccc2c1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]>>[OH;D1;+0:1]-[c:2](:[c:3]):[c:4]
72.2
[{"value": 72.0, "product": "C(C)OC(=O)C=1NC2=CC(=C(C=C2C1)O)Br", "details": "PERCENTYIELD", "is_desired": false}, {"value": 72.2, "product": "C(C)OC(=O)C=1NC2=CC(=C(C=C2C1)O)Br", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 8.30 g (27.8 mmol) 6-bromo-5-methoxy-1H-indole-2-carboxylic acid ethyl ester (prepared according to J. Org. Chem. 1974, 39, 3580) in 160 mL dichloromethane was cooled to −78° C. At this temperature, 55.7 mL boron tribromide (55.7 mmol; 1M solution in dichloromethane) were added. The solution was allowed t...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1ccc2[nH]ccc2c1
Other
ClCCl
null
null
CCOC(=O)c1cc2cc(OC)c(Br)cc2[nH]1>ClCCl>CCOC(=O)c1cc2cc(O)c(Br)cc2[nH]1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-da0d5627de604b18965097ada43a05cd
CC(C)N1CCC(Oc2cc3cc(C(=O)O)[nH]c3cc2Br)CC1.CS(=O)(=O)N1CCNCC1>>CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(C)(=O)=O)CC4)[nH]c3cc2Br)CC1
Cl.BrC1=C(C=C2C=C(NC2=C1)C(=O)O)OC1CCN(CC1)C(C)C.CS(=O)(=O)N1CCNCC1>>BrC1=C(C=C2C=C(NC2=C1)C(=O)N1CCN(CC1)S(=O)(=O)C)OC1CCN(CC1)C(C)C
O[C:14]([c:13]1[cH:12][c:11]2[cH:10][c:9]([O:8][CH:7]3[CH2:6][CH2:5][N:4]([CH:2]([CH3:1])[CH3:3])[CH2:32][CH2:31]3)[c:29]([Br:30])[cH:28][c:27]2[nH:26]1)=[O:15].[NH:16]1[CH2:17][CH2:18][N:19]([S:20]([CH3:21])(=[O:22])=[O:23])[CH2:24][CH2:25]1>>[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][c:11]3[c...
CC(C)N1CCC(Oc2cc3cc(C(=O)O)[nH]c3cc2Br)CC1.CS(=O)(=O)N1CCNCC1
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(C)(=O)=O)CC4)[nH]c3cc2Br)CC1
null
null
null
Acylation
Acylation of Nitrogen Nucleophiles by Carboxylic Acids
ed26ef5eea92a0cc433b3f89a34f4c61724425fa15a9d0ec83a0f7a903eec831
c5e4172490b2731ba9322b68af56376edadc31ce0bb9a3dfdea23a1817a852fd
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#7;a:5]:[c:6].[#7:7]1-[C:8]-[C:9]-[NH;D2;+0:10]-[C:11]-[C:12]-1>>[O;D1;H0:2]=[C;H0;D3;+0:1](-[N;H0;D3;+0:10]1-[C:9]-[C:8]-[#7:7]-[C:12]-[C:11]-1)-[c:3](:[c:4]):[#7;a:5]:[c:6]
45
[{"value": 45.0, "product": "BrC1=C(C=C2C=C(NC2=C1)C(=O)N1CCN(CC1)S(=O)(=O)C)OC1CCN(CC1)C(C)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The title compound was synthesized in analogy to example 1, from 6-bromo-5-(1-isopropyl-piperidin-4-yloxy)-1H-indole-2-carboxylic acid hydrochloride (example 1, intermediate a) and 1-methylsulfonyl-piperazine to afford the title compound as a light-yellow solid (45%). Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Secondary amine
Tertiary amide
C1CNCC[NH]1
C1C[NH]CC[NH]1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1
HO-
null
null
null
CC(C)N1CCC(Oc2cc3cc(C(=O)O)[nH]c3cc2Br)CC1.CS(=O)(=O)N1CCNCC1>>CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(C)(=O)=O)CC4)[nH]c3cc2Br)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-30cf47e103e547e6aad1f0f986f90b5c
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)N5CCCCC5)CC4)[nH]c3cc2Br)CC1.CC(C)OS(C)(=O)=O>>CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)N5CCCCC5)CC4)n(C(C)C)c3cc2Br)CC1
C([O-])(O)=O.[Na+].BrC1=C(C=C2C=C(NC2=C1)C(=O)N1CCN(CC1)S(=O)(=O)N1CCCCC1)OC1CCN(CC1)C(C)C.C([O-])([O-])=O.[Cs+].[Cs+].CS(=O)(=O)OC(C)C>>BrC1=C(C=C2C=C(N(C2=C1)C(C)C)C(=O)N1CCN(CC1)S(=O)(=O)N1CCCCC1)OC1CCN(CC1)C(C)C
[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][c:11]3[cH:12][c:13]([C:14](=[O:15])[N:16]4[CH2:17][CH2:18][N:19]([S:20](=[O:21])(=[O:22])[N:23]5[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]5)[CH2:29][CH2:30]4)[nH:31][c:35]3[cH:36][c:37]2[Br:38])[CH2:39][CH2:40]1.CS(=O)(=O)O[CH:32]([CH3:33])[CH3:34]>>[CH3...
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)N5CCCCC5)CC4)[nH]c3cc2Br)CC1.CC(C)OS(C)(=O)=O
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)N5CCCCC5)CC4)n(C(C)C)c3cc2Br)CC1
null
null
C(C)#N
Heteroatom Alkylation and Arylation
OtherReaction
d896e99f48a796a768d64b339abb5adbd8bc977c5bccdd47720d3a6657256b55
0b4f3c8c88df0a792d0db7d59004d7fe5681a61dd48ef2449ddca2d636f76ada
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCN(S(=O)(=O)N2CCCCC2)CC1
C-S(=O)(=O)-O-[CH;D3;+0:1](-[C;D1;H3:2])-[C;D1;H3:3].[C:4]-[#7:5](-[C:6](=[O;D1;H0:7])-[c:8]1:[c:9]:[c:10]:[c:11](:[c:12]):[nH;D2;+0:13]:1)-[C:14]>>[C:4]-[#7:5](-[C:6](=[O;D1;H0:7])-[c:8]1:[c:9]:[c:10]:[c:11](:[c:12]):[n;H0;D3;+0:13]:1-[CH;D3;+0:1](-[C;D1;H3:2])-[C;D1;H3:3])-[C:14]
56
[{"value": 56.0, "product": "BrC1=C(C=C2C=C(N(C2=C1)C(C)C)C(=O)N1CCN(CC1)S(=O)(=O)N1CCCCC1)OC1CCN(CC1)C(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 55.3, "product": "BrC1=C(C=C2C=C(N(C2=C1)C(C)C)C(=O)N1CCN(CC1)S(=O)(=O)N1CCCCC1)OC1CCN(CC1)C(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": f...
null
null
null
null
To a solution of 100 mg (0.17 mmol) [6-bromo-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-[4-(piperidine-1-sulfonyl)-piperazin-1-yl]-methanone (example 1) in 3 mL acetonitrile were added 109 mg (0.33 mmol) cesium carbonate and 46 mg (0.33 mmol) isopropyl methanesulfonate. The reaction was stirred under reflux for 1...
10.6084/m9.figshare.5104873.v1
null
Mesylate
null
c1ccc2[nH]ccc2c1
c1ccc2[nH]ccc2c1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1.C1CC[NH]CC1
MsOH.HO-
C(C)#N
null
null
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)N5CCCCC5)CC4)[nH]c3cc2Br)CC1.CC(C)OS(C)(=O)=O>C(C)#N>CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)N5CCCCC5)CC4)n(C(C)C)c3cc2Br)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-5f491590137e407ca62e853e1fef83e6
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)N5CCCCC5)CC4)[nH]c3cc2Br)CC1.OB(O)c1ccnc(Cl)c1>>CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)N5CCCCC5)CC4)n(-c4ccnc(Cl)c4)c3cc2Br)CC1
BrC1=C(C=C2C=C(NC2=C1)C(=O)N1CCN(CC1)S(=O)(=O)N1CCCCC1)OC1CCN(CC1)C(C)C.ClC1=NC=CC(=C1)B(O)O.N1=CC=CC=C1>>BrC1=C(C=C2C=C(N(C2=C1)C1=CC(=NC=C1)Cl)C(=O)N1CCN(CC1)S(=O)(=O)N1CCCCC1)OC1CCN(CC1)C(C)C
[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][c:11]3[cH:12][c:13]([C:14](=[O:15])[N:16]4[CH2:17][CH2:18][N:19]([S:20](=[O:21])(=[O:22])[N:23]5[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]5)[CH2:29][CH2:30]4)[nH:31][c:39]3[cH:40][c:41]2[Br:42])[CH2:43][CH2:44]1.OB(O)[c:32]1[cH:33][cH:34][n:35][c:36]([Cl...
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)N5CCCCC5)CC4)[nH]c3cc2Br)CC1.OB(O)c1ccnc(Cl)c1
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)N5CCCCC5)CC4)n(-c4ccnc(Cl)c4)c3cc2Br)CC1
null
C(C)(=O)[O-].[Cu+2].C(C)(=O)[O-]
C(Cl)(Cl)Cl
Heteroatom Alkylation and Arylation
OtherReaction
bb8efea1bfa0f318149646b016b0217e3f23a7e855502149afe40216d906e877
e0368246531386f86cd0aa9da1423eb47f529b782fb229563cefe1166d6ba4f5
O=C(c1cc2cc(OC3CCNCC3)ccc2n1-c1ccncc1)N1CCN(S(=O)(=O)N2CCCCC2)CC1
O-B(-O)-[c;H0;D3;+0:1]1:[c:2]:[c:3]:[#7;a:4]:[c:5](-[Cl;D1;H0:6]):[c:7]:1.[C:8]-[#7:9](-[C:10](=[O;D1;H0:11])-[c:12]1:[c:13]:[c:14]:[c:15](:[c:16]):[nH;D2;+0:17]:1)-[C:18]>>[C:8]-[#7:9](-[C:10](=[O;D1;H0:11])-[c:12]1:[c:13]:[c:14]:[c:15](:[c:16]):[n;H0;D3;+0:17]:1-[c;H0;D3;+0:1]1:[c:2]:[c:3]:[#7;a:4]:[c:5](-[Cl;D1;H0:6...
47.5
[{"value": 47.0, "product": "BrC1=C(C=C2C=C(N(C2=C1)C1=CC(=NC=C1)Cl)C(=O)N1CCN(CC1)S(=O)(=O)N1CCCCC1)OC1CCN(CC1)C(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 47.5, "product": "BrC1=C(C=C2C=C(N(C2=C1)C1=CC(=NC=C1)Cl)C(=O)N1CCN(CC1)S(=O)(=O)N1CCCCC1)OC1CCN(CC1)C(C)C", "details": "CALCULATEDPERCENTYIE...
35
CELSIUS
18
HOUR
A suspension of 0.15 g (0.25 mmol) [6-bromo-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-[4-(piperidine-1-sulfonyl)-piperazin-1-yl]-methanone (example 1), 119 mg (0.76 mmol) 2-chloropyridine-4-boronic acid, 91 mg (0.50 mmol) copper(II) acetate and 80 μL (78 mg, 1.0 mmol) pyridine in 4 ml chloroform was stirred 18 h...
10.6084/m9.figshare.5104873.v1
null
Boronic acid
null
c1ccc2[nH]ccc2c1.c1ccncc1
c1ccc2[nH]ccc2c1.c1ccncc1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1.C1CC[NH]CC1.c1ccncc1
HO-.B
C(C)(=O)[O-].[Cu+2].C(C)(=O)[O-].C(Cl)(Cl)Cl
35
18
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)N5CCCCC5)CC4)[nH]c3cc2Br)CC1.OB(O)c1ccnc(Cl)c1>C(C)(=O)[O-].[Cu+2].C(C)(=O)[O-].C(Cl)(Cl)Cl>CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)N5CCCCC5)CC4)n(-c4ccnc(Cl)c4)c3cc2Br)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-664e9c5a155c430cac4fb54f62b4950a
CCS(=O)(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)c(Br)cc3[nH]2)CC1.CS(=O)(=O)OCC(F)(F)F>>CCS(=O)(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)c(Br)cc3n2CC(F)(F)F)CC1
O.CS(=O)(=O)OCC(F)(F)F.BrC1=C(C=C2C=C(NC2=C1)C(=O)N1CCN(CC1)S(=O)(=O)CC)OC1CCN(CC1)C(C)C.[H-].[Na+]>>BrC1=C(C=C2C=C(N(C2=C1)CC(F)(F)F)C(=O)N1CCN(CC1)S(=O)(=O)CC)OC1CCN(CC1)C(C)C
[CH3:1][CH2:2][S:3](=[O:4])(=[O:5])[N:6]1[CH2:7][CH2:8][N:9]([C:10](=[O:11])[c:12]2[cH:13][c:14]3[cH:15][c:16]([O:17][CH:18]4[CH2:19][CH2:20][N:21]([CH:22]([CH3:23])[CH3:24])[CH2:25][CH2:26]4)[c:27]([Br:28])[cH:29][c:30]3[nH:31]2)[CH2:37][CH2:38]1.CS(=O)(=O)O[CH2:32][C:33]([F:34])([F:35])[F:36]>>[CH3:1][CH2:2][S:3](=[O...
CCS(=O)(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)c(Br)cc3[nH]2)CC1.CS(=O)(=O)OCC(F)(F)F
CCS(=O)(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)c(Br)cc3n2CC(F)(F)F)CC1
null
null
CN(C=O)C
Heteroatom Alkylation and Arylation
OtherReaction
d896e99f48a796a768d64b339abb5adbd8bc977c5bccdd47720d3a6657256b55
0b4f3c8c88df0a792d0db7d59004d7fe5681a61dd48ef2449ddca2d636f76ada
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
C-S(=O)(=O)-O-[CH2;D2;+0:1]-[C:2](-[F;D1;H0:3])(-[F;D1;H0:4])-[F;D1;H0:5].[C:6]-[#7:7](-[C:8](=[O;D1;H0:9])-[c:10]1:[c:11]:[c:12]:[c:13](:[c:14]):[nH;D2;+0:15]:1)-[C:16]>>[C:6]-[#7:7](-[C:8](=[O;D1;H0:9])-[c:10]1:[c:11]:[c:12]:[c:13](:[c:14]):[n;H0;D3;+0:15]:1-[CH2;D2;+0:1]-[C:2](-[F;D1;H0:3])(-[F;D1;H0:4])-[F;D1;H0:5]...
53
[{"value": 52.0, "product": "BrC1=C(C=C2C=C(N(C2=C1)CC(F)(F)F)C(=O)N1CCN(CC1)S(=O)(=O)CC)OC1CCN(CC1)C(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 53.0, "product": "BrC1=C(C=C2C=C(N(C2=C1)CC(F)(F)F)C(=O)N1CCN(CC1)S(=O)(=O)CC)OC1CCN(CC1)C(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false...
70
CELSIUS
15
MINUTE
To a solution of 144 mg (0.26 mmol) [6-bromo-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-(4-ethanesulfonyl-piperazin-1-yl)-methanone (example 10) in 3 mL N,N-dimethylformamide, were added 13 mg (0.29 mmol; 55% dispersion in mineral oil) sodium hydride. The reaction mixture was stirred 15 min at 70° C. 68 mg (0.29 ...
10.6084/m9.figshare.5104873.v1
null
Mesylate
null
c1ccc2[nH]ccc2c1
c1ccc2[nH]ccc2c1
C1C[NH]CC[NH]1.c1ccc2[nH]ccc2c1.C1CC[NH]CC1
MsOH.HO-
CN(C=O)C
70
0.25
CCS(=O)(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)c(Br)cc3[nH]2)CC1.CS(=O)(=O)OCC(F)(F)F>CN(C=O)C>CCS(=O)(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)c(Br)cc3n2CC(F)(F)F)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3ebb0e6b7e434129bfef22e8e0b9d4cf
CC(C)N1CCC(Oc2cc3cc(C(=O)O)[nH]c3cc2Br)CC1.O=S(=O)(N1CCNCC1)C(F)(F)F>>CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)C(F)(F)F)CC4)[nH]c3cc2Br)CC1
FC(S(=O)(=O)Cl)(F)F.BrC1=C(C=C2C=C(NC2=C1)C(=O)O)OC1CCN(CC1)C(C)C.Cl.FC(S(=O)(=O)N1CCNCC1)(F)F.N1(CCNCC1)C(=O)OC(C)(C)C>>BrC1=C(C=C2C=C(NC2=C1)C(=O)N1CCN(CC1)S(=O)(=O)C(F)(F)F)OC1CCN(CC1)C(C)C
O[C:14]([c:13]1[cH:12][c:11]2[cH:10][c:9]([O:8][CH:7]3[CH2:6][CH2:5][N:4]([CH:2]([CH3:1])[CH3:3])[CH2:35][CH2:34]3)[c:32]([Br:33])[cH:31][c:30]2[nH:29]1)=[O:15].[NH:16]1[CH2:17][CH2:18][N:19]([S:20](=[O:21])(=[O:22])[C:23]([F:24])([F:25])[F:26])[CH2:27][CH2:28]1>>[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c...
CC(C)N1CCC(Oc2cc3cc(C(=O)O)[nH]c3cc2Br)CC1.O=S(=O)(N1CCNCC1)C(F)(F)F
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)C(F)(F)F)CC4)[nH]c3cc2Br)CC1
null
null
null
Acylation
Acylation of Nitrogen Nucleophiles by Carboxylic Acids
ed26ef5eea92a0cc433b3f89a34f4c61724425fa15a9d0ec83a0f7a903eec831
c5e4172490b2731ba9322b68af56376edadc31ce0bb9a3dfdea23a1817a852fd
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#7;a:5]:[c:6].[#7:7]1-[C:8]-[C:9]-[NH;D2;+0:10]-[C:11]-[C:12]-1>>[O;D1;H0:2]=[C;H0;D3;+0:1](-[N;H0;D3;+0:10]1-[C:9]-[C:8]-[#7:7]-[C:12]-[C:11]-1)-[c:3](:[c:4]):[#7;a:5]:[c:6]
48
[{"value": 48.0, "product": "BrC1=C(C=C2C=C(NC2=C1)C(=O)N1CCN(CC1)S(=O)(=O)C(F)(F)F)OC1CCN(CC1)C(C)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The title compound was synthesized in analogy to example 1, from 6-bromo-5-(1-isopropyl-piperidin-4-yloxy)-1H-indole-2-carboxylic acid; hydrochloride (example 1, intermediate a) and 1-trifluoromethanesulfonyl-piperazine (prepared in analogy to International Patent Application Publ. No. WO 2003/064413 by using trifluoro...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Secondary amine
Tertiary amide
C1CNCC[NH]1
C1C[NH]CC[NH]1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1
HO-
null
null
null
CC(C)N1CCC(Oc2cc3cc(C(=O)O)[nH]c3cc2Br)CC1.O=S(=O)(N1CCNCC1)C(F)(F)F>>CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)C(F)(F)F)CC4)[nH]c3cc2Br)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-2200d6b7e9f94cecbba6c389b32d518b
CC(C)(C)OC(=O)N1CCNCC1.CC(C)N1CCC(Oc2cc3cc(C(=O)O)[nH]c3cc2Br)CC1.O=S(=O)(Cl)C1CC1>>CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)C5CC5)CC4)[nH]c3cc2Br)CC1
N1(CCNCC1)C(=O)OC(C)(C)C.Cl.BrC1=C(C=C2C=C(NC2=C1)C(=O)O)OC1CCN(CC1)C(C)C.C1(CC1)S(=O)(=O)N1CCNCC1.C1(CC1)S(=O)(=O)Cl>>BrC1=C(C=C2C=C(NC2=C1)C(=O)N1CCN(CC1)S(=O)(=O)C1CC1)OC1CCN(CC1)C(C)C
CC(C)(C)OC(=O)[N:19]1[CH2:18][CH2:17][NH:16][CH2:27][CH2:26]1.O[C:14]([c:13]1[cH:12][c:11]2[cH:10][c:9]([O:8][CH:7]3[CH2:6][CH2:5][N:4]([CH:2]([CH3:1])[CH3:3])[CH2:34][CH2:33]3)[c:31]([Br:32])[cH:30][c:29]2[nH:28]1)=[O:15].Cl[S:20](=[O:21])(=[O:22])[CH:23]1[CH2:24][CH2:25]1>>[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][C...
CC(C)(C)OC(=O)N1CCNCC1.CC(C)N1CCC(Oc2cc3cc(C(=O)O)[nH]c3cc2Br)CC1.O=S(=O)(Cl)C1CC1
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)C5CC5)CC4)[nH]c3cc2Br)CC1
null
null
null
Acylation
OtherReaction
46aac7e0c5bae0c4b10c58b3e54bdd310ee6376094e059179d0bdbb508b434b4
dd0d2994de79b42478fa7896ad0a1953280227920b0d81bb2d39f8ceafa61163
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCN(S(=O)(=O)C2CC2)CC1
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-[S;H0;D4;+0:7](=[O;D1;H0:8])(=[O;D1;H0:9])-[C:10]1-[C:11]-[C:12]-1.O-[C;H0;D3;+0:13](=[O;D1;H0:14])-[c:15](:[c:16]):[#7;a:17]:[c:18]>>[O;D1;H0:14]=[C;H0;D3;+0:13](-[N;H0;D3;+0:4]1-[C:3]-[C:2]-[N;H0;D3;+0:1](-[S;H0;D4;+0:7](=[O;D1;H0:8])(=[O;D...
62
[{"value": 62.0, "product": "BrC1=C(C=C2C=C(NC2=C1)C(=O)N1CCN(CC1)S(=O)(=O)C1CC1)OC1CCN(CC1)C(C)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The title compound was synthesized in analogy to example 1, from 6-bromo-5-(1-isopropyl-piperidin-4-yloxy)-1H-indole-2-carboxylic acid hydrochloride (example 1, intermediate a) and cyclopropylsulfonyl-piperazine (prepared in analogy to International Patent Application Publ. No. WO 2003/064413 by using cyclopropylsulfon...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Carboxylic acid.Ether.Secondary amine.Sulfonyl halide.Boc
Tertiary amide.Tertiary amine
C1C[NH]CCN1
C1C[NH]CC[NH]1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1.C1CC1
HCl
null
null
null
CC(C)(C)OC(=O)N1CCNCC1.CC(C)N1CCC(Oc2cc3cc(C(=O)O)[nH]c3cc2Br)CC1.O=S(=O)(Cl)C1CC1>>CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)C5CC5)CC4)[nH]c3cc2Br)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-e69e3bf0f3a64f0d91ae797b41304377
CC(C)N1CCC(Oc2cc3cc(C(=O)O)[nH]c3cc2Br)CC1.O=C(C1CC1)N1CCNCC1>>CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(C(=O)C5CC5)CC4)[nH]c3cc2Br)CC1
Cl.BrC1=C(C=C2C=C(NC2=C1)C(=O)O)OC1CCN(CC1)C(C)C.C1(CC1)C(=O)N1CCNCC1>>BrC1=C(C=C2C=C(NC2=C1)C(=O)N1CCN(CC1)C(=O)C1CC1)OC1CCN(CC1)C(C)C
O[C:14]([c:13]1[cH:12][c:11]2[cH:10][c:9]([O:8][CH:7]3[CH2:6][CH2:5][N:4]([CH:2]([CH3:1])[CH3:3])[CH2:33][CH2:32]3)[c:30]([Br:31])[cH:29][c:28]2[nH:27]1)=[O:15].[NH:16]1[CH2:17][CH2:18][N:19]([C:20](=[O:21])[CH:22]2[CH2:23][CH2:24]2)[CH2:25][CH2:26]1>>[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][...
CC(C)N1CCC(Oc2cc3cc(C(=O)O)[nH]c3cc2Br)CC1.O=C(C1CC1)N1CCNCC1
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(C(=O)C5CC5)CC4)[nH]c3cc2Br)CC1
null
null
null
Acylation
Acylation of Nitrogen Nucleophiles by Carboxylic Acids
ed26ef5eea92a0cc433b3f89a34f4c61724425fa15a9d0ec83a0f7a903eec831
c5e4172490b2731ba9322b68af56376edadc31ce0bb9a3dfdea23a1817a852fd
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCN(C(=O)C2CC2)CC1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#7;a:5]:[c:6].[#7:7]1-[C:8]-[C:9]-[NH;D2;+0:10]-[C:11]-[C:12]-1>>[O;D1;H0:2]=[C;H0;D3;+0:1](-[N;H0;D3;+0:10]1-[C:9]-[C:8]-[#7:7]-[C:12]-[C:11]-1)-[c:3](:[c:4]):[#7;a:5]:[c:6]
48
[{"value": 48.0, "product": "BrC1=C(C=C2C=C(NC2=C1)C(=O)N1CCN(CC1)C(=O)C1CC1)OC1CCN(CC1)C(C)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The title compound was synthesized in analogy to example 1, from 6-bromo-5-(1-isopropyl-piperidin-4-yloxy)-1H-indole-2-carboxylic acid hydrochloride (example 1, intermediate a) and 1-(cyclopropanecarbonyl)piperazine to afford the title compound as a light-yellow foam (48%). Conditions: See reaction.notes.procedure_deta...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Secondary amine
Tertiary amide
C1CNCC[NH]1
C1C[NH]CC[NH]1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1.C1CC1
HO-
null
null
null
CC(C)N1CCC(Oc2cc3cc(C(=O)O)[nH]c3cc2Br)CC1.O=C(C1CC1)N1CCNCC1>>CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(C(=O)C5CC5)CC4)[nH]c3cc2Br)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3b3e5c9eadae4f55acaf58a8096343cf
CC(=O)N1CCNCC1.CC(C)N1CCC(Oc2cc3cc(C(=O)O)[nH]c3cc2Br)CC1>>CC(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)c(Br)cc3[nH]2)CC1
Cl.BrC1=C(C=C2C=C(NC2=C1)C(=O)O)OC1CCN(CC1)C(C)C.C(C)(=O)N1CCNCC1>>BrC1=C(C=C2C=C(NC2=C1)C(=O)N1CCN(CC1)C(C)=O)OC1CCN(CC1)C(C)C
[CH3:1][C:2](=[O:3])[N:4]1[CH2:5][CH2:6][NH:7][CH2:30][CH2:31]1.O[C:8](=[O:9])[c:10]1[cH:11][c:12]2[cH:13][c:14]([O:15][CH:16]3[CH2:17][CH2:18][N:19]([CH:20]([CH3:21])[CH3:22])[CH2:23][CH2:24]3)[c:25]([Br:26])[cH:27][c:28]2[nH:29]1>>[CH3:1][C:2](=[O:3])[N:4]1[CH2:5][CH2:6][N:7]([C:8](=[O:9])[c:10]2[cH:11][c:12]3[cH:13]...
CC(=O)N1CCNCC1.CC(C)N1CCC(Oc2cc3cc(C(=O)O)[nH]c3cc2Br)CC1
CC(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)c(Br)cc3[nH]2)CC1
null
null
null
Acylation
Acylation of Nitrogen Nucleophiles by Carboxylic Acids
be4b86020a065d99e289e528d425e25dd0737bea0f2fd81bb05a4d03f92a7d75
c5e4172490b2731ba9322b68af56376edadc31ce0bb9a3dfdea23a1817a852fd
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#7;a:5]:[c:6].[#7:7]1-[C:8]-[C:9]-[NH;D2;+0:10]-[C:11]-[C:12]-1>>[O;D1;H0:2]=[C;H0;D3;+0:1](-[N;H0;D3;+0:10]1-[C:9]-[C:8]-[#7:7]-[C:12]-[C:11]-1)-[c:3](:[c:4]):[#7;a:5]:[c:6]
52
[{"value": 52.0, "product": "BrC1=C(C=C2C=C(NC2=C1)C(=O)N1CCN(CC1)C(C)=O)OC1CCN(CC1)C(C)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The title compound was synthesized in analogy to example 1, from 6-bromo-5-(1-isopropyl-piperidin-4-yloxy)-1H-indole-2-carboxylic acid hydrochloride (example 1, intermediate a) and 1-acetylpiperazine to afford the title compound as a light-yellow foam (52%). Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Secondary amine
Tertiary amide
C1C[NH]CCN1
C1C[NH]CC[NH]1
C1C[NH]CC[NH]1.c1ccc2[nH]ccc2c1.C1CC[NH]CC1
HO-
null
null
null
CC(=O)N1CCNCC1.CC(C)N1CCC(Oc2cc3cc(C(=O)O)[nH]c3cc2Br)CC1>>CC(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)c(Br)cc3[nH]2)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-5cd740228ca8414e86fd02cc422b5198
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)C5CC5)CC4)n(CCO[Si](C)(C)C(C)(C)C)c3cc2Br)CC1>>CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)C5CC5)CC4)n(CCO)c3cc2Br)CC1
BrC1=C(C=C2C=C(N(C2=C1)CCO[Si](C)(C)C(C)(C)C)C(=O)N1CCN(CC1)S(=O)(=O)C1CC1)OC1CCN(CC1)C(C)C.FC(C(=O)O)(F)F>>BrC1=C(C=C2C=C(N(C2=C1)CCO)C(=O)N1CCN(CC1)S(=O)(=O)C1CC1)OC1CCN(CC1)C(C)C
CC(C)(C)[Si](C)(C)[O:31][CH2:30][CH2:29][n:28]1[c:13]([C:14](=[O:15])[N:16]2[CH2:17][CH2:18][N:19]([S:20](=[O:21])(=[O:22])[CH:23]3[CH2:24][CH2:25]3)[CH2:26][CH2:27]2)[cH:12][c:11]2[cH:10][c:9]([O:8][CH:7]3[CH2:6][CH2:5][N:4]([CH:2]([CH3:1])[CH3:3])[CH2:37][CH2:36]3)[c:34]([Br:35])[cH:33][c:32]21>>[CH3:1][CH:2]([CH3:3]...
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)C5CC5)CC4)n(CCO[Si](C)(C)C(C)(C)C)c3cc2Br)CC1
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)C5CC5)CC4)n(CCO)c3cc2Br)CC1
null
null
ClCCl
Deprotection
Alcohol deprotection from silyl ethers
6ff8c9c41093ab5237b871dd4689ba6431022d615e227d3774901a983c846e4b
84d9f5b4e7757c58e584c26c7d52c9a3f594fbcb0c0d22f34765a93a932fcd5b
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCN(S(=O)(=O)C2CC2)CC1
C-C(-C)(-C)-[Si](-C)(-C)-[O;H0;D2;+0:1]-[C:2]-[C:3]>>[C:3]-[C:2]-[OH;D1;+0:1]
99
[{"value": 99.0, "product": "BrC1=C(C=C2C=C(N(C2=C1)CCO)C(=O)N1CCN(CC1)S(=O)(=O)C1CC1)OC1CCN(CC1)C(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 99.0, "product": "BrC1=C(C=C2C=C(N(C2=C1)CCO)C(=O)N1CCN(CC1)S(=O)(=O)C1CC1)OC1CCN(CC1)C(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
A solution of 85 mg (0.12 mmol) [6-bromo-1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-(4-cyclopropanesulfonyl-piperazin-1-yl)-methanone in 2 mL dichloromethane was cooled to 0° C. and 1.0 mL (1.49 g, 13.1 mmol) trifluoroacetic acid were added. The cooling bath was remove...
10.6084/m9.figshare.5104873.v1
null
TMS ether protective group
Primary alcohol
null
null
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1.C1CC1
Other
ClCCl
null
1
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)C5CC5)CC4)n(CCO[Si](C)(C)C(C)(C)C)c3cc2Br)CC1>ClCCl>CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)C5CC5)CC4)n(CCO)c3cc2Br)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-900d663f816341dd876527062f41434b
CC(C)(C)[Si](C)(C)OCCBr.CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)C5CC5)CC4)[nH]c3cc2Br)CC1>>CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)C5CC5)CC4)n(CCO[Si](C)(C)C(C)(C)C)c3cc2Br)CC1
BrC1=C(C=C2C=C(NC2=C1)C(=O)N1CCN(CC1)S(=O)(=O)C1CC1)OC1CCN(CC1)C(C)C.[H-].[Na+].BrCCO[Si](C)(C)C(C)(C)C>>BrC1=C(C=C2C=C(N(C2=C1)CCO[Si](C)(C)C(C)(C)C)C(=O)N1CCN(CC1)S(=O)(=O)C1CC1)OC1CCN(CC1)C(C)C
Br[CH2:29][CH2:30][O:31][Si:32]([CH3:33])([CH3:34])[C:35]([CH3:36])([CH3:37])[CH3:38].[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][c:11]3[cH:12][c:13]([C:14](=[O:15])[N:16]4[CH2:17][CH2:18][N:19]([S:20](=[O:21])(=[O:22])[CH:23]5[CH2:24][CH2:25]5)[CH2:26][CH2:27]4)[nH:28][c:39]3[cH:40][c:41]2[Br:4...
CC(C)(C)[Si](C)(C)OCCBr.CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)C5CC5)CC4)[nH]c3cc2Br)CC1
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)C5CC5)CC4)n(CCO[Si](C)(C)C(C)(C)C)c3cc2Br)CC1
null
null
CN(C=O)C
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
92cc004fc3e2a92f5c9aa0385cdf93f1126e35d5aa485f4f5fe9240c9543c8fe
2e1e5fd9557b69cb528f6b2ffd179c67ef24ecb1a2c3994e1cdf0efe7ae19e9c
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCN(S(=O)(=O)C2CC2)CC1
Br-[CH2;D2;+0:1]-[C:2]-[#8:3].[C:4]-[#7:5](-[C:6](=[O;D1;H0:7])-[c:8]1:[c:9]:[c:10]:[c:11](:[c:12]):[nH;D2;+0:13]:1)-[C:14]>>[#8:3]-[C:2]-[CH2;D2;+0:1]-[n;H0;D3;+0:13]1:[c:8](-[C:6](=[O;D1;H0:7])-[#7:5](-[C:4])-[C:14]):[c:9]:[c:10]:[c:11]:1:[c:12]
36
[{"value": 36.0, "product": "BrC1=C(C=C2C=C(N(C2=C1)CCO[Si](C)(C)C(C)(C)C)C(=O)N1CCN(CC1)S(=O)(=O)C1CC1)OC1CCN(CC1)C(C)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The title compound was prepared in analogy to example 12, from [6-bromo-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-(4-cyclopropanesulfonyl-piperazin-1-yl)-methanone (example 17), sodium hydride and (2-bromoethoxy)-tert-butyldimethylsilane in N,N-dimethylformamide, to afford the title compound as a colourless foam...
10.6084/m9.figshare.5104873.v1
null
Primary halide
null
c1ccc2[nH]ccc2c1
c1ccc2[nH]ccc2c1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1.C1CC1
HBr
CN(C=O)C
null
null
CC(C)(C)[Si](C)(C)OCCBr.CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)C5CC5)CC4)[nH]c3cc2Br)CC1>CN(C=O)C>CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)C5CC5)CC4)n(CCO[Si](C)(C)C(C)(C)C)c3cc2Br)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-045bbf6a327c481b8dd1b5f284784d98
CS(=O)(=O)N1CCNCC1.Cc1cc2[nH]c(C(=O)O)cc2cc1OC1CCN(C(C)C)CC1>>Cc1cc2[nH]c(C(=O)N3CCN(S(C)(=O)=O)CC3)cc2cc1OC1CCN(C(C)C)CC1
Cl.C(C)(C)N1CCC(CC1)OC=1C=C2C=C(NC2=CC1C)C(=O)O.CS(=O)(=O)N1CCNCC1>>C(C)(C)N1CCC(CC1)OC=1C=C2C=C(NC2=CC1C)C(=O)N1CCN(CC1)S(=O)(=O)C
[NH:9]1[CH2:10][CH2:11][N:12]([S:13]([CH3:14])(=[O:15])=[O:16])[CH2:17][CH2:18]1.O[C:7]([c:6]1[nH:5][c:4]2[cH:3][c:2]([CH3:1])[c:22]([O:23][CH:24]3[CH2:25][CH2:26][N:27]([CH:28]([CH3:29])[CH3:30])[CH2:31][CH2:32]3)[cH:21][c:20]2[cH:19]1)=[O:8]>>[CH3:1][c:2]1[cH:3][c:4]2[nH:5][c:6]([C:7](=[O:8])[N:9]3[CH2:10][CH2:11][N:...
CS(=O)(=O)N1CCNCC1.Cc1cc2[nH]c(C(=O)O)cc2cc1OC1CCN(C(C)C)CC1
Cc1cc2[nH]c(C(=O)N3CCN(S(C)(=O)=O)CC3)cc2cc1OC1CCN(C(C)C)CC1
null
null
null
Acylation
Acylation of Nitrogen Nucleophiles by Carboxylic Acids
ed26ef5eea92a0cc433b3f89a34f4c61724425fa15a9d0ec83a0f7a903eec831
c5e4172490b2731ba9322b68af56376edadc31ce0bb9a3dfdea23a1817a852fd
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#7;a:5]:[c:6].[#7:7]1-[C:8]-[C:9]-[NH;D2;+0:10]-[C:11]-[C:12]-1>>[O;D1;H0:2]=[C;H0;D3;+0:1](-[N;H0;D3;+0:10]1-[C:9]-[C:8]-[#7:7]-[C:12]-[C:11]-1)-[c:3](:[c:4]):[#7;a:5]:[c:6]
49
[{"value": 49.0, "product": "C(C)(C)N1CCC(CC1)OC=1C=C2C=C(NC2=CC1C)C(=O)N1CCN(CC1)S(=O)(=O)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The title compound was synthesized in analogy to example 1, from 5-(1-isopropyl-piperidin-4-yloxy)-6-methyl-1H-indole-2-carboxylic acid hydrochloride and 1-methanesulfonylpiperazine to afford the title compound as a light-yellow solid (49%). Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Secondary amine
Tertiary amide
C1CNCC[NH]1
C1C[NH]CC[NH]1
c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1.C1CC[NH]CC1
HO-
null
null
null
CS(=O)(=O)N1CCNCC1.Cc1cc2[nH]c(C(=O)O)cc2cc1OC1CCN(C(C)C)CC1>>Cc1cc2[nH]c(C(=O)N3CCN(S(C)(=O)=O)CC3)cc2cc1OC1CCN(C(C)C)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-bdc9eaeae824466c8063ebed2b0bdb5d
CC(C)N1CCC(O)CC1.CCOC(=O)c1cc2cc(O)c(C)cc2[nH]1>>CCOC(=O)c1cc2cc(OC3CCN(C(C)C)CC3)c(C)cc2[nH]1
N(=NC(=O)OC(C)(C)C)C(=O)OC(C)(C)C.C(C)OC(=O)C=1NC2=CC(=C(C=C2C1)O)C.C(C)(C)N1CCC(CC1)O.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1>>C(C)OC(=O)C=1NC2=CC(=C(C=C2C1)OC1CCN(CC1)C(C)C)C
O[CH:12]1[CH2:13][CH2:14][N:15]([CH:16]([CH3:17])[CH3:18])[CH2:19][CH2:20]1.[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]2[cH:9][c:10]([OH:11])[c:21]([CH3:22])[cH:23][c:24]2[nH:25]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]2[cH:9][c:10]([O:11][CH:12]3[CH2:13][CH2:14][N:15]([CH:16]([CH3:17])[CH3:18])[CH2:19...
CC(C)N1CCC(O)CC1.CCOC(=O)c1cc2cc(O)c(C)cc2[nH]1
CCOC(=O)c1cc2cc(OC3CCN(C(C)C)CC3)c(C)cc2[nH]1
null
null
O1CCCC1
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
a9e936b0e9135225700edbab1c7696738b7f1f0756494b6ceeeda63b184d572f
776ba735002e33225fbc578943016110c2c43efefd97bfeea4ec3cc2e2e1532f
c1cc2cc(OC3CCNCC3)ccc2[nH]1
O-[CH;D3;+0:1]1-[C:2]-[C:3]-[#7:4]-[C:5]-[C:6]-1.[OH;D1;+0:7]-[c:8](:[c:9]):[c:10]>>[c:9]:[c:8](-[O;H0;D2;+0:7]-[CH;D3;+0:1]1-[C:2]-[C:3]-[#7:4]-[C:5]-[C:6]-1):[c:10]
38
[{"value": 38.0, "product": "C(C)OC(=O)C=1NC2=CC(=C(C=C2C1)OC1CCN(CC1)C(C)C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 37.7, "product": "C(C)OC(=O)C=1NC2=CC(=C(C=C2C1)OC1CCN(CC1)C(C)C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
18
HOUR
To a suspension of 0.125 g (0.57 mmol) 5-hydroxy-6-methyl-1H-indole-2-carboxylic acid ethyl ester in 3 mL tetrahydrofuran, 98 mg (0.68 mmol) 1-isopropyl-piperidin-4-ol and 0.18 g (0.68 mmol) triphenylphosphine were added. The reaction was cooled to 0° C., 0.16 g (0.68 mmol) di-tert-butyl azodicarboxylate were added and...
10.6084/m9.figshare.5104873.v1
null
Secondary alcohol.Aromatic alcohol
Ether
C1CC[NH]CC1
C1CC[NH]CC1
c1ccc2[nH]ccc2c1.C1CC[NH]CC1
HO-
O1CCCC1
0
18
CC(C)N1CCC(O)CC1.CCOC(=O)c1cc2cc(O)c(C)cc2[nH]1>O1CCCC1>CCOC(=O)c1cc2cc(OC3CCN(C(C)C)CC3)c(C)cc2[nH]1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-83b1e8e5275742b29be9677410a23816
CCOC(=O)c1cc2cc(OC)c(C)cc2[nH]1>>CCOC(=O)c1cc2cc(O)c(C)cc2[nH]1
C(C)OC(=O)C=1NC2=CC(=C(C=C2C1)OC)C.B(Br)(Br)Br>>C(C)OC(=O)C=1NC2=CC(=C(C=C2C1)O)C
C[O:11][c:10]1[cH:9][c:8]2[cH:7][c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[nH:16][c:15]2[cH:14][c:12]1[CH3:13]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]2[cH:9][c:10]([OH:11])[c:12]([CH3:13])[cH:14][c:15]2[nH:16]1
CCOC(=O)c1cc2cc(OC)c(C)cc2[nH]1
CCOC(=O)c1cc2cc(O)c(C)cc2[nH]1
null
null
ClCCl
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc2[nH]ccc2c1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]>>[OH;D1;+0:1]-[c:2](:[c:3]):[c:4]
43.2
[{"value": 43.0, "product": "C(C)OC(=O)C=1NC2=CC(=C(C=C2C1)O)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 43.2, "product": "C(C)OC(=O)C=1NC2=CC(=C(C=C2C1)O)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
A solution of 0.13 g (0.56 mmol) 5-methoxy-6-methyl-1H-indole-2-carboxylic acid ethyl ester in 3 mL dichloromethane was cooled to −78° C. 1.11 mL (1.1 mmol, 1 M solution in dichloromethane) boron tribromide were added and the cooling bath was removed. After stirring 2 h at room temperature, the solution was poured into...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1ccc2[nH]ccc2c1
Other
ClCCl
null
2
CCOC(=O)c1cc2cc(OC)c(C)cc2[nH]1>ClCCl>CCOC(=O)c1cc2cc(O)c(C)cc2[nH]1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-d044932258fe475c8040a0b2971784b8
CCOC(=O)c1cc2cc(OC)c(C)cc2n1C(=O)OC(C)(C)C>>CCOC(=O)c1cc2cc(OC)c(C)cc2[nH]1
CCOC(=O)C=1N(C2=CC(=C(C=C2C1)OC)C)C(=O)OC(C)(C)C.FC(C(=O)O)(F)F>>C(C)OC(=O)C=1NC2=CC(=C(C=C2C1)OC)C
CC(C)(C)OC(=O)[n:17]1[c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[cH:7][c:8]2[cH:9][c:10]([O:11][CH3:12])[c:13]([CH3:14])[cH:15][c:16]21>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]2[cH:9][c:10]([O:11][CH3:12])[c:13]([CH3:14])[cH:15][c:16]2[nH:17]1
CCOC(=O)c1cc2cc(OC)c(C)cc2n1C(=O)OC(C)(C)C
CCOC(=O)c1cc2cc(OC)c(C)cc2[nH]1
null
null
ClCCl
Reduction
Boc amine deprotection
2e722145961e6ed684a4057199869eba686866962dedad6b4f68c70e9c6154ea
e1bf5a54b1f87284564f107662531aec2aff7de801e4606340967b38924afb28
c1ccc2[nH]ccc2c1
C-C(-C)(-C)-O-C(=O)-[n;H0;D3;+0:1]1:[c:2](:[c:3]):[c:4]:[c:5]:[c:6]:1-[C:7](=[O;D1;H0:8])-[#8:9]-[C:10]>>[C:10]-[#8:9]-[C:7](=[O;D1;H0:8])-[c:6]1:[c:5]:[c:4]:[c:2](:[c:3]):[nH;D2;+0:1]:1
97
[{"value": 97.0, "product": "C(C)OC(=O)C=1NC2=CC(=C(C=C2C1)OC)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
A solution of 0.20 g (0.60 mmol) 5-methoxy-6-methyl-indole-1,2-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester in 4 mL dichloromethane was cooled to 0° C. and 2 mL (3.0 g, 26.1 mmol) trifluoroacetic acid were added. The ice bath was removed and after stirring 1 h at room temperature the solution was evaporated to dr...
10.6084/m9.figshare.5104873.v1
null
Ether.Boc
null
c1ccc2[nH]ccc2c1
c1ccc2[nH]ccc2c1
c1ccc2[nH]ccc2c1
HO-
ClCCl
null
1
CCOC(=O)c1cc2cc(OC)c(C)cc2n1C(=O)OC(C)(C)C>ClCCl>CCOC(=O)c1cc2cc(OC)c(C)cc2[nH]1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-e60f90ba2ed04fd082d42f89de8183e3
CCOC(=O)c1cc2cc(OC)c(Br)cc2n1C(=O)OC(C)(C)C>>CCOC(=O)c1cc2cc(OC)c(C)cc2n1C(=O)OC(C)(C)C
C([O-])(O)=O.[Na+].CCOC(=O)C=1N(C2=CC(=C(C=C2C1)OC)Br)C(=O)OC(C)(C)C.CB1OB(OB(O1)C)C.C([O-])([O-])=O.[Na+].[Na+]>>CCOC(=O)C=1N(C2=CC(=C(C=C2C1)OC)C)C(=O)OC(C)(C)C
Br[c:13]1[c:10]([O:11][CH3:12])[cH:9][c:8]2[cH:7][c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[n:17]([C:18](=[O:19])[O:20][C:21]([CH3:22])([CH3:23])[CH3:24])[c:16]2[cH:15]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]2[cH:9][c:10]([O:11][CH3:12])[c:13]([CH3:14])[cH:15][c:16]2[n:17]1[C:18](=[O:19])[O:20][C:21]([CH3:22])...
CCOC(=O)c1cc2cc(OC)c(Br)cc2n1C(=O)OC(C)(C)C
CCOC(=O)c1cc2cc(OC)c(C)cc2n1C(=O)OC(C)(C)C
null
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1
O.COCCOC.C(C)(=O)OCC
Functional Group Interconversion
OtherReaction
dbd18d2678064f1f36b138b22466f91ec2b8ad6433b033470409c1d945c1e16a
56de34d4a44cb25d9380269ee5e138b0f24b40a3a0db22c5508049dc775a861f
c1ccc2[nH]ccc2c1
Br-[c;H0;D3;+0:1]1:[c:2]:[c:3](:[c:4]:[c:5]:[c:6]:1-[#8:7]):[#7;a:8](-[C:9](-[#8:10])=[O;D1;H0:11]):[c:12]-[C:13](-[#8:14])=[O;D1;H0:15]>>[#8:7]-[c:6]1:[c:5]:[c:4]:[c:3](:[c:2]:[c;H0;D3;+0:1]:1-[C;D1;H3:16]):[#7;a:8](-[C:9](-[#8:10])=[O;D1;H0:11]):[c:12]-[C:13](-[#8:14])=[O;D1;H0:15]
57
[{"value": 57.0, "product": "CCOC(=O)C=1N(C2=CC(=C(C=C2C1)OC)C)C(=O)OC(C)(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 57.0, "product": "CCOC(=O)C=1N(C2=CC(=C(C=C2C1)OC)C)C(=O)OC(C)(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
30
MINUTE
To a solution of 0.20 g (0.50 mmol) 6-bromo-5-methoxy-indole-1,2-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester in 8 mL 1,2-dimethoxyethane were added 58 μg (0.050 mmol) tetrakis(triphenylphosphine)palladium(0). After stirring 30 min at room temperature, 76 μg (0.60 mmol) trimethylboroxine and 0.16 g (1.50 mmol) so...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
null
c1ccc2[nH]ccc2c1
c1ccc2[nH]ccc2c1
c1ccc2[nH]ccc2c1
null
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.O.COCCOC.C(C)(=O)OCC
null
0.5
CCOC(=O)c1cc2cc(OC)c(Br)cc2n1C(=O)OC(C)(C)C>C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.O.COCCOC.C(C)(=O)OCC>CCOC(=O)c1cc2cc(OC)c(C)cc2n1C(=O)OC(C)(C)C
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-dd0394a8216149ca803701f59b103fc6
CCOC(=O)N1CCNCC1.Cc1cc2[nH]c(C(=O)O)cc2cc1OC1CCN(C(C)C)CC1>>CCOC(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)c(C)cc3[nH]2)CC1
Cl.C(C)(C)N1CCC(CC1)OC=1C=C2C=C(NC2=CC1C)C(=O)O.C(C)OC(=O)N1CCNCC1>>C(C)OC(=O)N1CCN(CC1)C(=O)C=1NC2=CC(=C(C=C2C1)OC1CCN(CC1)C(C)C)C
[CH3:1][CH2:2][O:3][C:4](=[O:5])[N:6]1[CH2:7][CH2:8][NH:9][CH2:32][CH2:33]1.O[C:10](=[O:11])[c:12]1[cH:13][c:14]2[cH:15][c:16]([O:17][CH:18]3[CH2:19][CH2:20][N:21]([CH:22]([CH3:23])[CH3:24])[CH2:25][CH2:26]3)[c:27]([CH3:28])[cH:29][c:30]2[nH:31]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[N:6]1[CH2:7][CH2:8][N:9]([C:10](=[O:11]...
CCOC(=O)N1CCNCC1.Cc1cc2[nH]c(C(=O)O)cc2cc1OC1CCN(C(C)C)CC1
CCOC(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)c(C)cc3[nH]2)CC1
null
null
null
Acylation
Acylation of Nitrogen Nucleophiles by Carboxylic Acids
be4b86020a065d99e289e528d425e25dd0737bea0f2fd81bb05a4d03f92a7d75
c5e4172490b2731ba9322b68af56376edadc31ce0bb9a3dfdea23a1817a852fd
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#7;a:5]:[c:6].[#7:7]1-[C:8]-[C:9]-[NH;D2;+0:10]-[C:11]-[C:12]-1>>[O;D1;H0:2]=[C;H0;D3;+0:1](-[N;H0;D3;+0:10]1-[C:9]-[C:8]-[#7:7]-[C:12]-[C:11]-1)-[c:3](:[c:4]):[#7;a:5]:[c:6]
65
[{"value": 65.0, "product": "C(C)OC(=O)N1CCN(CC1)C(=O)C=1NC2=CC(=C(C=C2C1)OC1CCN(CC1)C(C)C)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The title compound was synthesized in analogy to example 1, from 5-(1-isopropyl-piperidin-4-yloxy)-6-methyl-1H-indole-2-carboxylic acid hydrochloride and 1-ethoxycarbonylpiperazine to afford the title compound as a light-yellow foam (65%). Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Secondary amine
Tertiary amide
C1C[NH]CCN1
C1C[NH]CC[NH]1
C1C[NH]CC[NH]1.c1ccc2[nH]ccc2c1.C1CC[NH]CC1
HO-
null
null
null
CCOC(=O)N1CCNCC1.Cc1cc2[nH]c(C(=O)O)cc2cc1OC1CCN(C(C)C)CC1>>CCOC(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)c(C)cc3[nH]2)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-9f84cf9092984fa5987f0277e691be2b
Cc1cc2[nH]c(C(=O)O)cc2cc1OC1CCN(C(C)C)CC1.O=C(C1CC1)N1CCNCC1>>Cc1cc2[nH]c(C(=O)N3CCN(C(=O)C4CC4)CC3)cc2cc1OC1CCN(C(C)C)CC1
Cl.C(C)(C)N1CCC(CC1)OC=1C=C2C=C(NC2=CC1C)C(=O)O.C1(CC1)C(=O)N1CCNCC1>>C1(CC1)C(=O)N1CCN(CC1)C(=O)C=1NC2=CC(=C(C=C2C1)OC1CCN(CC1)C(C)C)C
O[C:7]([c:6]1[nH:5][c:4]2[cH:3][c:2]([CH3:1])[c:23]([O:24][CH:25]3[CH2:26][CH2:27][N:28]([CH:29]([CH3:30])[CH3:31])[CH2:32][CH2:33]3)[cH:22][c:21]2[cH:20]1)=[O:8].[NH:9]1[CH2:10][CH2:11][N:12]([C:13](=[O:14])[CH:15]2[CH2:16][CH2:17]2)[CH2:18][CH2:19]1>>[CH3:1][c:2]1[cH:3][c:4]2[nH:5][c:6]([C:7](=[O:8])[N:9]3[CH2:10][CH...
Cc1cc2[nH]c(C(=O)O)cc2cc1OC1CCN(C(C)C)CC1.O=C(C1CC1)N1CCNCC1
Cc1cc2[nH]c(C(=O)N3CCN(C(=O)C4CC4)CC3)cc2cc1OC1CCN(C(C)C)CC1
null
null
null
Acylation
Acylation of Nitrogen Nucleophiles by Carboxylic Acids
ed26ef5eea92a0cc433b3f89a34f4c61724425fa15a9d0ec83a0f7a903eec831
c5e4172490b2731ba9322b68af56376edadc31ce0bb9a3dfdea23a1817a852fd
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCN(C(=O)C2CC2)CC1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#7;a:5]:[c:6].[#7:7]1-[C:8]-[C:9]-[NH;D2;+0:10]-[C:11]-[C:12]-1>>[O;D1;H0:2]=[C;H0;D3;+0:1](-[N;H0;D3;+0:10]1-[C:9]-[C:8]-[#7:7]-[C:12]-[C:11]-1)-[c:3](:[c:4]):[#7;a:5]:[c:6]
56
[{"value": 56.0, "product": "C1(CC1)C(=O)N1CCN(CC1)C(=O)C=1NC2=CC(=C(C=C2C1)OC1CCN(CC1)C(C)C)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The title compound was synthesized in analogy to example 1, from 5-(1-isopropyl-piperidin-4-yloxy)-6-methyl-1H-indole-2-carboxylic acid hydrochloride and 1-(cyclopropanecarbonyl)piperazine to afford the title compound as a light-yellow foam (56%). Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Secondary amine
Tertiary amide
C1CNCC[NH]1
C1C[NH]CC[NH]1
c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1.C1CC1.C1CC[NH]CC1
HO-
null
null
null
Cc1cc2[nH]c(C(=O)O)cc2cc1OC1CCN(C(C)C)CC1.O=C(C1CC1)N1CCNCC1>>Cc1cc2[nH]c(C(=O)N3CCN(C(=O)C4CC4)CC3)cc2cc1OC1CCN(C(C)C)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-181aad76998c4b76a9cc21cbd335fd4f
CC(C)OS(C)(=O)=O.Cc1cc2[nH]c(C(=O)N3CCN(S(C)(=O)=O)CC3)cc2cc1OC1CCN(C(C)C)CC1>>Cc1cc2c(cc1OC1CCN(C(C)C)CC1)cc(C(=O)N1CCN(S(C)(=O)=O)CC1)n2C(C)C
C(C)(C)N1CCC(CC1)OC=1C=C2C=C(NC2=CC1C)C(=O)N1CCN(CC1)S(=O)(=O)C.C([O-])([O-])=O.[Cs+].[Cs+].CS(=O)(=O)OC(C)C>>C(C)(C)N1C(=CC2=CC(=C(C=C12)C)OC1CCN(CC1)C(C)C)C(=O)N1CCN(CC1)S(=O)(=O)C
CS(=O)(=O)O[CH:33]([CH3:34])[CH3:35].[CH3:1][c:2]1[cH:3][c:4]2[c:5]([cH:6][c:7]1[O:8][CH:9]1[CH2:10][CH2:11][N:12]([CH:13]([CH3:14])[CH3:15])[CH2:16][CH2:17]1)[cH:18][c:19]([C:20](=[O:21])[N:22]1[CH2:23][CH2:24][N:25]([S:26]([CH3:27])(=[O:28])=[O:29])[CH2:30][CH2:31]1)[nH:32]2>>[CH3:1][c:2]1[cH:3][c:4]2[c:5]([cH:6][c:7...
CC(C)OS(C)(=O)=O.Cc1cc2[nH]c(C(=O)N3CCN(S(C)(=O)=O)CC3)cc2cc1OC1CCN(C(C)C)CC1
Cc1cc2c(cc1OC1CCN(C(C)C)CC1)cc(C(=O)N1CCN(S(C)(=O)=O)CC1)n2C(C)C
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
d896e99f48a796a768d64b339abb5adbd8bc977c5bccdd47720d3a6657256b55
0b4f3c8c88df0a792d0db7d59004d7fe5681a61dd48ef2449ddca2d636f76ada
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
C-S(=O)(=O)-O-[CH;D3;+0:1](-[C;D1;H3:2])-[C;D1;H3:3].[C:4]-[#7:5](-[C:6](=[O;D1;H0:7])-[c:8]1:[c:9]:[c:10]:[c:11](:[c:12]):[nH;D2;+0:13]:1)-[C:14]>>[C:4]-[#7:5](-[C:6](=[O;D1;H0:7])-[c:8]1:[c:9]:[c:10]:[c:11](:[c:12]):[n;H0;D3;+0:13]:1-[CH;D3;+0:1](-[C;D1;H3:2])-[C;D1;H3:3])-[C:14]
9
[{"value": 9.0, "product": "C(C)(C)N1C(=CC2=CC(=C(C=C12)C)OC1CCN(CC1)C(C)C)C(=O)N1CCN(CC1)S(=O)(=O)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The title compound was synthesized in analogy to example 4, from [5-(1-isopropyl-piperidin-4-yloxy)-6-methyl-1H-indol-2-yl]-(4-methanesulfonyl-piperazin-1-yl)-methanone (example 29), cesium carbonate and isopropyl methanesulfonate, to afford the title compound as a light-yellow oil (9%). Conditions: See reaction.notes....
10.6084/m9.figshare.5104873.v1
null
Mesylate
null
c1ccc2[nH]ccc2c1
c1ccc2[nH]ccc2c1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1
MsOH.HO-
null
null
null
CC(C)OS(C)(=O)=O.Cc1cc2[nH]c(C(=O)N3CCN(S(C)(=O)=O)CC3)cc2cc1OC1CCN(C(C)C)CC1>>Cc1cc2c(cc1OC1CCN(C(C)C)CC1)cc(C(=O)N1CCN(S(C)(=O)=O)CC1)n2C(C)C
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-738d11a3f8a34cebbe5ca2ff2b99cedf
CC(C)(C)OC(=O)N1CCNCC1.CC(C)N1CCC(Oc2cc3cc(C(=O)O)[nH]c3cc2Cl)CC1>>CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(C(=O)OC(C)(C)C)CC4)[nH]c3cc2Cl)CC1
Cl.ClC1=C(C=C2C=C(NC2=C1)C(=O)O)OC1CCN(CC1)C(C)C.[Cl-].[Li+].C(C)(C)(C)OC(=O)N1CCNCC1.F[B-](F)(F)F.N1(N=NC2=C1C=CC=C2)OC(=[N+](C)C)N(C)C.C(C)(C)N(C(C)C)CC>>C(C)(C)(C)OC(=O)N1CCN(CC1)C(=O)C=1NC2=CC(=C(C=C2C1)OC1CCN(CC1)C(C)C)Cl
[NH:16]1[CH2:17][CH2:18][N:19]([C:20](=[O:21])[O:22][C:23]([CH3:24])([CH3:25])[CH3:26])[CH2:27][CH2:28]1.O[C:14]([c:13]1[cH:12][c:11]2[cH:10][c:9]([O:8][CH:7]3[CH2:6][CH2:5][N:4]([CH:2]([CH3:1])[CH3:3])[CH2:35][CH2:34]3)[c:32]([Cl:33])[cH:31][c:30]2[nH:29]1)=[O:15]>>[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8...
CC(C)(C)OC(=O)N1CCNCC1.CC(C)N1CCC(Oc2cc3cc(C(=O)O)[nH]c3cc2Cl)CC1
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(C(=O)OC(C)(C)C)CC4)[nH]c3cc2Cl)CC1
null
null
CN(C=O)C
Acylation
Acylation of Nitrogen Nucleophiles by Carboxylic Acids
ed26ef5eea92a0cc433b3f89a34f4c61724425fa15a9d0ec83a0f7a903eec831
c5e4172490b2731ba9322b68af56376edadc31ce0bb9a3dfdea23a1817a852fd
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#7;a:5]:[c:6].[#7:7]1-[C:8]-[C:9]-[NH;D2;+0:10]-[C:11]-[C:12]-1>>[O;D1;H0:2]=[C;H0;D3;+0:1](-[N;H0;D3;+0:10]1-[C:9]-[C:8]-[#7:7]-[C:12]-[C:11]-1)-[c:3](:[c:4]):[#7;a:5]:[c:6]
57
[{"value": 57.0, "product": "C(C)(C)(C)OC(=O)N1CCN(CC1)C(=O)C=1NC2=CC(=C(C=C2C1)OC1CCN(CC1)C(C)C)Cl", "details": "PERCENTYIELD", "is_desired": false}]
null
null
20
HOUR
A mixture of 6-chloro-5-(1-isopropyl-piperidin-4-yloxy)-1H-indole-2-carboxylic acid hydrochloride salt with 1 eq. lithium chloride (760 mg, 1.0 eq.), tert-butyl-1-piperazinecarboxylate (467 mg, 1.25 eq.), O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (838 mg, 1.25 eq.) and N,N-diisopropylethylami...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Secondary amine
Tertiary amide
C1CNCC[NH]1
C1C[NH]CC[NH]1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1
HO-
CN(C=O)C
null
20
CC(C)(C)OC(=O)N1CCNCC1.CC(C)N1CCC(Oc2cc3cc(C(=O)O)[nH]c3cc2Cl)CC1>CN(C=O)C>CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(C(=O)OC(C)(C)C)CC4)[nH]c3cc2Cl)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3bc6f73e9bb3468996e0477624b39e75
CC(C)N1CCC(O)CC1.CCOC(=O)c1cc2cc(O)c(Cl)cc2[nH]1>>CCOC(=O)c1cc2cc(OC3CCN(C(C)C)CC3)c(Cl)cc2[nH]1
C(C)OC(=O)C=1NC2=CC(=C(C=C2C1)O)Cl.C(C)(C)N1CCC(CC1)O.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.CC(C)(C)OC(=O)/N=N/C(=O)OC(C)(C)C>>C(C)OC(=O)C=1NC2=CC(=C(C=C2C1)OC1CCN(CC1)C(C)C)Cl
O[CH:12]1[CH2:13][CH2:14][N:15]([CH:16]([CH3:17])[CH3:18])[CH2:19][CH2:20]1.[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]2[cH:9][c:10]([OH:11])[c:21]([Cl:22])[cH:23][c:24]2[nH:25]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]2[cH:9][c:10]([O:11][CH:12]3[CH2:13][CH2:14][N:15]([CH:16]([CH3:17])[CH3:18])[CH2:19]...
CC(C)N1CCC(O)CC1.CCOC(=O)c1cc2cc(O)c(Cl)cc2[nH]1
CCOC(=O)c1cc2cc(OC3CCN(C(C)C)CC3)c(Cl)cc2[nH]1
null
null
O1CCCC1
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
a9e936b0e9135225700edbab1c7696738b7f1f0756494b6ceeeda63b184d572f
776ba735002e33225fbc578943016110c2c43efefd97bfeea4ec3cc2e2e1532f
c1cc2cc(OC3CCNCC3)ccc2[nH]1
O-[CH;D3;+0:1]1-[C:2]-[C:3]-[#7:4]-[C:5]-[C:6]-1.[OH;D1;+0:7]-[c:8](:[c:9]):[c:10]>>[c:9]:[c:8](-[O;H0;D2;+0:7]-[CH;D3;+0:1]1-[C:2]-[C:3]-[#7:4]-[C:5]-[C:6]-1):[c:10]
67
[{"value": 67.0, "product": "C(C)OC(=O)C=1NC2=CC(=C(C=C2C1)OC1CCN(CC1)C(C)C)Cl", "details": "PERCENTYIELD", "is_desired": false}, {"value": 66.7, "product": "C(C)OC(=O)C=1NC2=CC(=C(C=C2C1)OC1CCN(CC1)C(C)C)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
20
HOUR
To a cold (0° C.) mixture of 6-chloro-5-hydroxy-1H-indole-2-carboxylic acid ethyl ester (625 mg, 1.0 eq.), 1-Isopropyl-piperidin-4-ol (448 mg, 1.2 eq.) and triphenylphosphine (846 mg, 1.2 eq.) in tetrahydrofuran (8 mL) was added dropwise a solution of di-tert-butylazodicarboxylate (725 mg, 1.2 eq.) in tetrahydrofuran (...
10.6084/m9.figshare.5104873.v1
null
Secondary alcohol.Aromatic alcohol
Ether
C1CC[NH]CC1
C1CC[NH]CC1
c1ccc2[nH]ccc2c1.C1CC[NH]CC1
HO-
O1CCCC1
null
20
CC(C)N1CCC(O)CC1.CCOC(=O)c1cc2cc(O)c(Cl)cc2[nH]1>O1CCCC1>CCOC(=O)c1cc2cc(OC3CCN(C(C)C)CC3)c(Cl)cc2[nH]1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-2fa291c04abe4df0ac9941ccc6fda1bc
CCOC(=O)c1cc2cc(OC)c(Cl)cc2[nH]1>>CCOC(=O)c1cc2cc(O)c(Cl)cc2[nH]1
B(Br)(Br)Br.C(C)OC(=O)C=1NC2=CC(=C(C=C2C1)OC)Cl>>C(C)OC(=O)C=1NC2=CC(=C(C=C2C1)O)Cl
C[O:11][c:10]1[cH:9][c:8]2[cH:7][c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[nH:16][c:15]2[cH:14][c:12]1[Cl:13]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]2[cH:9][c:10]([OH:11])[c:12]([Cl:13])[cH:14][c:15]2[nH:16]1
CCOC(=O)c1cc2cc(OC)c(Cl)cc2[nH]1
CCOC(=O)c1cc2cc(O)c(Cl)cc2[nH]1
null
null
ClCCl
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc2[nH]ccc2c1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]>>[OH;D1;+0:1]-[c:2](:[c:3]):[c:4]
74.6
[{"value": 74.0, "product": "C(C)OC(=O)C=1NC2=CC(=C(C=C2C1)O)Cl", "details": "PERCENTYIELD", "is_desired": false}, {"value": 74.6, "product": "C(C)OC(=O)C=1NC2=CC(=C(C=C2C1)O)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
To a cooled (−78° C.) solution of 6-chloro-5-methoxy-1H-indole-2-carboxylic acid ethyl ester (930 mg, 1.0 eq.) in dichloromethane (20 mL), was slowly added a 1M solution of boron tribromide in dichloromethane (7.33 mL, 2.0 eq.). The mixture was stirred at room temperature for 1 h, partitioned between ethyl acetate and ...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1ccc2[nH]ccc2c1
Other
ClCCl
null
1
CCOC(=O)c1cc2cc(OC)c(Cl)cc2[nH]1>ClCCl>CCOC(=O)c1cc2cc(O)c(Cl)cc2[nH]1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-04b9f57d0cd4482a9aa02d8215ee1801
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(C(=O)OC(C)(C)C)CC4)[nH]c3cc2Cl)CC1>>CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCNCC4)[nH]c3cc2Cl)CC1
C(C)(C)(C)OC(=O)N1CCN(CC1)C(=O)C=1NC2=CC(=C(C=C2C1)OC1CCN(CC1)C(C)C)Cl.FC(C(=O)O)(F)F>>ClC1=C(C=C2C=C(NC2=C1)C(=O)N1CCNCC1)OC1CCN(CC1)C(C)C
CC(C)(C)OC(=O)[N:19]1[CH2:18][CH2:17][N:16]([C:14]([c:13]2[cH:12][c:11]3[cH:10][c:9]([O:8][CH:7]4[CH2:6][CH2:5][N:4]([CH:2]([CH3:1])[CH3:3])[CH2:28][CH2:27]4)[c:25]([Cl:26])[cH:24][c:23]3[nH:22]2)=[O:15])[CH2:21][CH2:20]1>>[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][c:11]3[cH:12][c:13]([C:14](=[...
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(C(=O)OC(C)(C)C)CC4)[nH]c3cc2Cl)CC1
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCNCC4)[nH]c3cc2Cl)CC1
null
null
ClCCl
Reduction
Boc amine deprotection
2c25e19aee181a3c5131cfdfda27035fd54d4379a11d745dfb75d386bacfd500
a94b29c7264c852156fc1cdd4a0951a4fc26c06d0edc9e50c743825dbf79e3fd
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)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>>[#7:4]1-[C:3]-[C:2]-[NH;D2;+0:1]-[C:6]-[C:5]-1
94.2
[{"value": 94.0, "product": "ClC1=C(C=C2C=C(NC2=C1)C(=O)N1CCNCC1)OC1CCN(CC1)C(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 94.2, "product": "ClC1=C(C=C2C=C(NC2=C1)C(=O)N1CCNCC1)OC1CCN(CC1)C(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3
HOUR
To a cold (0° C.) solution of 4-[6-chloro-5-(1-isopropyl-piperidin-4-yloxy)-1H-indole-2-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester (example 3, 547 mg, 1.0 eq.) in dichloromethane was added trifluoroacetic acid (1.23 mL, 10 eq.) dropwise. The reaction mixture was stirred 3 h at room temperature. The mixture...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Secondary amine
C1C[NH]CC[NH]1
C1C[NH]CCN1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CCN1
HO-
ClCCl
null
3
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(C(=O)OC(C)(C)C)CC4)[nH]c3cc2Cl)CC1>ClCCl>CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCNCC4)[nH]c3cc2Cl)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-74d069b74f2c4196b99f3e8b80128187
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCNCC4)[nH]c3cc2Cl)CC1.O=C(Cl)C1CC1>>CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(C(=O)C5CC5)CC4)[nH]c3cc2Cl)CC1
ClC1=C(C=C2C=C(NC2=C1)C(=O)N1CCNCC1)OC1CCN(CC1)C(C)C.C([O-])([O-])=O.[Cs+].[Cs+].C1(CC1)C(=O)Cl>>ClC1=C(C=C2C=C(NC2=C1)C(=O)N1CCN(CC1)C(=O)C1CC1)OC1CCN(CC1)C(C)C
[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][c:11]3[cH:12][c:13]([C:14](=[O:15])[N:16]4[CH2:17][CH2:18][NH:19][CH2:25][CH2:26]4)[nH:27][c:28]3[cH:29][c:30]2[Cl:31])[CH2:32][CH2:33]1.Cl[C:20](=[O:21])[CH:22]1[CH2:23][CH2:24]1>>[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][c:1...
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCNCC4)[nH]c3cc2Cl)CC1.O=C(Cl)C1CC1
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(C(=O)C5CC5)CC4)[nH]c3cc2Cl)CC1
null
null
C(C)#N
Acylation
N-alkylation of secondary amines with alkyl halides
008ee4368afbd52034630a2410a1738f53049b314574435184e4e0be81b96642
96cb0a2fed10552c5770a45a2d6523b47ac3e38928b4a9c698d8577451182dcd
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCN(C(=O)C2CC2)CC1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]1-[C:4]-[C:5]-1.[#7:6]1-[C:7]-[C:8]-[NH;D2;+0:9]-[C:10]-[C:11]-1>>[O;D1;H0:2]=[C;H0;D3;+0:1](-[C:3]1-[C:4]-[C:5]-1)-[N;H0;D3;+0:9]1-[C:8]-[C:7]-[#7:6]-[C:11]-[C:10]-1
46
[{"value": 46.0, "product": "ClC1=C(C=C2C=C(NC2=C1)C(=O)N1CCN(CC1)C(=O)C1CC1)OC1CCN(CC1)C(C)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
To a mixture of [6-chloro-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-piperazin-1-yl-methanone (example 36, 150 mg, 1.0 eq.) and cesium carbonate (243 mg, 2.0 eq.) in acetonitrile (8 mL) was added cyclopropane carbonylchloride. The reaction mixture was refluxed 4 h. The reaction mixture was concentrated in vacuo a...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Secondary amine
Tertiary amide
C1C[NH]CCN1
C1C[NH]CC[NH]1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1.C1CC1
HCl
C(C)#N
null
null
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCNCC4)[nH]c3cc2Cl)CC1.O=C(Cl)C1CC1>C(C)#N>CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(C(=O)C5CC5)CC4)[nH]c3cc2Cl)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-4737d552c37844098816d5044b23a439
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCNCC4)[nH]c3cc2Cl)CC1.CN(C)C(=O)Cl>>CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(C(=O)N(C)C)CC4)[nH]c3cc2Cl)CC1
ClC1=C(C=C2C=C(NC2=C1)C(=O)N1CCNCC1)OC1CCN(CC1)C(C)C.CN(C(=O)Cl)C>>CN(C(=O)N1CCN(CC1)C(=O)C=1NC2=CC(=C(C=C2C1)OC1CCN(CC1)C(C)C)Cl)C
[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][c:11]3[cH:12][c:13]([C:14](=[O:15])[N:16]4[CH2:17][CH2:18][NH:19][CH2:25][CH2:26]4)[nH:27][c:28]3[cH:29][c:30]2[Cl:31])[CH2:32][CH2:33]1.Cl[C:20](=[O:21])[N:22]([CH3:23])[CH3:24]>>[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][c:11...
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCNCC4)[nH]c3cc2Cl)CC1.CN(C)C(=O)Cl
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(C(=O)N(C)C)CC4)[nH]c3cc2Cl)CC1
null
null
null
Acylation
N-alkylation of secondary amines with alkyl halides
dcfba2aa7ca13a6ccdf0aa9e5554d01dee20f5aad8e3132e302a663220e425bb
353c6e1db25433862a8bcf26ca332f6abeb45cb685806584bc65f8cfcb712540
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#7:3](-[C;D1;H3:4])-[C;D1;H3:5].[#7:6]1-[C:7]-[C:8]-[NH;D2;+0:9]-[C:10]-[C:11]-1>>[C;D1;H3:4]-[#7:3](-[C;D1;H3:5])-[C;H0;D3;+0:1](=[O;D1;H0:2])-[N;H0;D3;+0:9]1-[C:8]-[C:7]-[#7:6]-[C:11]-[C:10]-1
62
[{"value": 62.0, "product": "CN(C(=O)N1CCN(CC1)C(=O)C=1NC2=CC(=C(C=C2C1)OC1CCN(CC1)C(C)C)Cl)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The title compound was synthesized in analogy to example 37, from [6-chloro-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-piperazin-1-yl-methanone (example 36), and dimethylcarbamoyl chloride, to afford the title compound as a light-yellow solid (62%). Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Tertiary amide.Secondary amine
Urea
C1C[NH]CCN1
C1C[NH]CC[NH]1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1
HCl
null
null
null
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCNCC4)[nH]c3cc2Cl)CC1.CN(C)C(=O)Cl>>CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(C(=O)N(C)C)CC4)[nH]c3cc2Cl)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-7a69c1e2624c4d73a131dc376e992407
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCNCC4)[nH]c3cc2Cl)CC1.CS(=O)(=O)Cl>>CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(C)(=O)=O)CC4)[nH]c3cc2Cl)CC1
ClC1=C(C=C2C=C(NC2=C1)C(=O)N1CCNCC1)OC1CCN(CC1)C(C)C.CS(=O)(=O)Cl>>ClC1=C(C=C2C=C(NC2=C1)C(=O)N1CCN(CC1)S(=O)(=O)C)OC1CCN(CC1)C(C)C
[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][c:11]3[cH:12][c:13]([C:14](=[O:15])[N:16]4[CH2:17][CH2:18][NH:19][CH2:24][CH2:25]4)[nH:26][c:27]3[cH:28][c:29]2[Cl:30])[CH2:31][CH2:32]1.Cl[S:20]([CH3:21])(=[O:22])=[O:23]>>[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][c:11]3[cH:1...
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCNCC4)[nH]c3cc2Cl)CC1.CS(=O)(=O)Cl
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(C)(=O)=O)CC4)[nH]c3cc2Cl)CC1
null
null
null
Acylation
Sulfonamide synthesis (Schotten-Baumann) secondary amine
c6a995ab9be6571957febbe378833244177e30fd671e64e4e1ffe6f50345cf56
b7aca5a5d690b0846685a854bc946849e1041bfc3965161290b5ffb2821af09e
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
Cl-[S;H0;D4;+0:1](-[C;D1;H3:2])(=[O;D1;H0:3])=[O;D1;H0:4].[#7:5]1-[C:6]-[C:7]-[NH;D2;+0:8]-[C:9]-[C:10]-1>>[C;D1;H3:2]-[S;H0;D4;+0:1](=[O;D1;H0:3])(=[O;D1;H0:4])-[N;H0;D3;+0:8]1-[C:7]-[C:6]-[#7:5]-[C:10]-[C:9]-1
72
[{"value": 72.0, "product": "ClC1=C(C=C2C=C(NC2=C1)C(=O)N1CCN(CC1)S(=O)(=O)C)OC1CCN(CC1)C(C)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The title compound was synthesized in analogy to example 37, from [6-chloro-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-piperazin-1-yl-methanone (example 36), and methanesulfonyl chloride, to afford the title compound as an off-white solid (72%). Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Secondary amine.Sulfonyl halide
Tertiary amine
C1C[NH]CCN1
C1C[NH]CC[NH]1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1
HCl
null
null
null
CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCNCC4)[nH]c3cc2Cl)CC1.CS(=O)(=O)Cl>>CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(C)(=O)=O)CC4)[nH]c3cc2Cl)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-1c31bd3c5b534ffe8922bc3315a8f7d6
CC(C)(C)OC(=O)N1CCNCC1.O=S(=O)(Cl)c1ccc(C(F)(F)F)cc1>>Cl.O=S(=O)(c1ccc(C(F)(F)F)cc1)N1CCNCC1
C(C)(C)(C)OC(=O)N1CCNCC1.C(C)N(CC)CC.FC(C1=CC=C(C=C1)S(=O)(=O)Cl)(F)F>>Cl.FC(C1=CC=C(C=C1)S(=O)(=O)N1CCNCC1)(F)F
CC(C)(C)OC(=O)[N:15]1[CH2:16][CH2:17][NH:18][CH2:19][CH2:20]1.[Cl:1][S:3](=[O:2])(=[O:4])[c:5]1[cH:6][cH:7][c:8]([C:9]([F:10])([F:11])[F:12])[cH:13][cH:14]1>>[ClH:1].[O:2]=[S:3](=[O:4])([c:5]1[cH:6][cH:7][c:8]([C:9]([F:10])([F:11])[F:12])[cH:13][cH:14]1)[N:15]1[CH2:16][CH2:17][NH:18][CH2:19][CH2:20]1
CC(C)(C)OC(=O)N1CCNCC1.O=S(=O)(Cl)c1ccc(C(F)(F)F)cc1
Cl.O=S(=O)(c1ccc(C(F)(F)F)cc1)N1CCNCC1
null
null
ClCCl
Acylation
OtherReaction
fe80f4ba0030540fe0dd5c07c99df28cb9dc1f06dbe0a7382338f606945d5f85
705725ff5b1b5bdebe12db390e8895152ae89941b9a07e00716e981f5b25c654
O=S(=O)(c1ccccc1)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;H0;D1;+0:7]-[S;H0;D4;+0:8](=[O;D1;H0:9])(=[O;D1;H0:10])-[c:11](:[c:12]):[c:13]>>[ClH;D0;+0:7].[O;D1;H0:9]=[S;H0;D4;+0:8](=[O;D1;H0:10])(-[N;H0;D3;+0:1]1-[C:2]-[C:3]-[#7:4]-[C:5]-[C:6]-1)-[c:11](:[c:12]):[c:13]
31.4
[{"value": 31.0, "product": "Cl.FC(C1=CC=C(C=C1)S(=O)(=O)N1CCNCC1)(F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 31.4, "product": "Cl.FC(C1=CC=C(C=C1)S(=O)(=O)N1CCNCC1)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
To a solution of N-tert-butyloxycarbonylpiperazine (1.00 g, 5.37 mmol) in dichloromethane were added triethylamine (1.05 eq, 0.78 ml) and 4-(trifluoromethyl)-benzenesulfonyl chloride (1.02 eq, 1.345 g). The mixture was stirred overnight at room temperature, diluted with dichloromethane, washed with aqueous sodium bicar...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Sulfonyl halide.Boc
Tertiary amine
C1C[NH]CCN1
C1C[NH]CCN1
c1ccccc1.C1C[NH]CCN1
HO-
ClCCl
null
8
CC(C)(C)OC(=O)N1CCNCC1.O=S(=O)(Cl)c1ccc(C(F)(F)F)cc1>ClCCl>Cl.O=S(=O)(c1ccc(C(F)(F)F)cc1)N1CCNCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-2328382c02c04eac95bd1adb49588ef6
CC(C)(C)OC(=O)N1CCNCC1.CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)O)cc3c2)CC1>>CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCN(C(=O)OC(C)(C)C)CC4)cc3c2)CC1
CC(C)N1CCC(CC1)OC=1C=C2C=C(NC2=CC1)C(=O)O.C(C)(C)(C)OC(=O)N1CCNCC1>>C(C)(C)(C)OC(=O)N1CCN(CC1)C(=O)C=1NC2=CC=C(C=C2C1)OC1CCN(CC1)C(C)C
[NH:17]1[CH2:18][CH2:19][N:20]([C:21](=[O:22])[O:23][C:24]([CH3:25])([CH3:26])[CH3:27])[CH2:28][CH2:29]1.O[C:15]([c:14]1[nH:13][c:12]2[cH:11][cH:10][c:9]([O:8][CH:7]3[CH2:6][CH2:5][N:4]([CH:2]([CH3:1])[CH3:3])[CH2:34][CH2:33]3)[cH:32][c:31]2[cH:30]1)=[O:16]>>[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[...
CC(C)(C)OC(=O)N1CCNCC1.CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)O)cc3c2)CC1
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCN(C(=O)OC(C)(C)C)CC4)cc3c2)CC1
null
null
null
Acylation
Acylation of Nitrogen Nucleophiles by Carboxylic Acids
ed26ef5eea92a0cc433b3f89a34f4c61724425fa15a9d0ec83a0f7a903eec831
c5e4172490b2731ba9322b68af56376edadc31ce0bb9a3dfdea23a1817a852fd
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#7;a:5]:[c:6].[#7:7]1-[C:8]-[C:9]-[NH;D2;+0:10]-[C:11]-[C:12]-1>>[O;D1;H0:2]=[C;H0;D3;+0:1](-[N;H0;D3;+0:10]1-[C:9]-[C:8]-[#7:7]-[C:12]-[C:11]-1)-[c:3](:[c:4]):[#7;a:5]:[c:6]
null
[]
null
null
null
null
The title compound was prepared in analogy to example 40b), from 5-[[1-(1-methylethyl)-4-piperidinyl]oxy]-1H-Indole-2-carboxylic acid and 1-(tert-butoxycarbonyl)piperazine. Light-yellow solid. MS (m/z): 471.1 (M+H)+. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Secondary amine
Tertiary amide
C1CNCC[NH]1
C1C[NH]CC[NH]1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1
HO-
null
null
null
CC(C)(C)OC(=O)N1CCNCC1.CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)O)cc3c2)CC1>>CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCN(C(=O)OC(C)(C)C)CC4)cc3c2)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-adfe3d9336b84d1ba1667c8e82b797e0
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCNCC4)cc3c2)CC1.CS(=O)(=O)Cl>>CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCN(S(C)(=O)=O)CC4)cc3c2)CC1
Cl.Cl.C(C)(C)N1CCC(CC1)OC=1C=C2C=C(NC2=CC1)C(=O)N1CCNCC1.C(C)N(CC)CC.CS(=O)(=O)Cl>>C(C)(C)N1CCC(CC1)OC=1C=C2C=C(NC2=CC1)C(=O)N1CCN(CC1)S(=O)(=O)C
[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][cH:11][c:12]3[nH:13][c:14]([C:15](=[O:16])[N:17]4[CH2:18][CH2:19][NH:20][CH2:25][CH2:26]4)[cH:27][c:28]3[cH:29]2)[CH2:30][CH2:31]1.Cl[S:21]([CH3:22])(=[O:23])=[O:24]>>[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][cH:11][c:12]3[nH:...
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCNCC4)cc3c2)CC1.CS(=O)(=O)Cl
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCN(S(C)(=O)=O)CC4)cc3c2)CC1
null
null
ClCCl
Acylation
Sulfonamide synthesis (Schotten-Baumann) secondary amine
c6a995ab9be6571957febbe378833244177e30fd671e64e4e1ffe6f50345cf56
b7aca5a5d690b0846685a854bc946849e1041bfc3965161290b5ffb2821af09e
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
Cl-[S;H0;D4;+0:1](-[C;D1;H3:2])(=[O;D1;H0:3])=[O;D1;H0:4].[#7:5]1-[C:6]-[C:7]-[NH;D2;+0:8]-[C:9]-[C:10]-1>>[C;D1;H3:2]-[S;H0;D4;+0:1](=[O;D1;H0:3])(=[O;D1;H0:4])-[N;H0;D3;+0:8]1-[C:7]-[C:6]-[#7:5]-[C:10]-[C:9]-1
null
[]
null
null
8
HOUR
To a solution of [5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-piperazin-1-yl-methanone dihydrochloride (82 mg, 0.22 mmol) in dichloromethane (2 ml) were added triethylamine (4.2 eq, 0.13 ml) and methanesulfonyl chloride (1.4 eq, 0.02 ml). The mixture was stirred overnight, diluted with dichloromethane and washed w...
10.6084/m9.figshare.5104873.v1
null
Secondary amine.Sulfonyl halide
Tertiary amine
C1C[NH]CCN1
C1C[NH]CC[NH]1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1
HCl
ClCCl
null
8
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCNCC4)cc3c2)CC1.CS(=O)(=O)Cl>ClCCl>CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCN(S(C)(=O)=O)CC4)cc3c2)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-15d79e8205704d0b8c8c4122d786cc89
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCN(C(=O)OC(C)(C)C)CC4)cc3c2)CC1>>CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCNCC4)cc3c2)CC1.Cl
C(C)OCC.C(C)(C)(C)OC(=O)N1CCN(CC1)C(=O)C=1NC2=CC=C(C=C2C1)OC1CCN(CC1)C(C)C.Cl>>Cl.Cl.C(C)(C)N1CCC(CC1)OC=1C=C2C=C(NC2=CC1)C(=O)N1CCNCC1
CC(C)(C)OC(=O)[N:20]1[CH2:19][CH2:18][N:17]([C:15]([c:14]2[nH:13][c:12]3[cH:11][cH:10][c:9]([O:8][CH:7]4[CH2:6][CH2:5][N:4]([CH:2]([CH3:1])[CH3:3])[CH2:27][CH2:26]4)[cH:25][c:24]3[cH:23]2)=[O:16])[CH2:22][CH2:21]1>>[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][cH:11][c:12]3[nH:13][c:14]([C:15](=[O...
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCN(C(=O)OC(C)(C)C)CC4)cc3c2)CC1
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCNCC4)cc3c2)CC1.Cl
null
null
C(C)(=O)OCC
Miscellaneous
Boc amine deprotection
ca9288c3be1743ea424604bf62770990eec893f8f7f07c612f680fef8b15531e
c95e79e18f8ea11cf22745e0eab38cab98566b1b63e7d80ee200f4cb4f94f00c
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)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>>[#7:4]1-[C:3]-[C:2]-[NH;D2;+0:1]-[C:6]-[C:5]-1
null
[]
null
null
72
HOUR
A solution of 4-[5-(1-isopropyl-piperidin-4-yloxy)-1H-indole-2-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester (800 mg, 1.7 mmol) in ethyl acetate (25 ml) was treated with hydrogen chloride (5M in ethyl acetate, 12 ml) and the mixture stirred 72 h at room temperature. The resulting suspension was cooled to 0° C...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Secondary amine
C1C[NH]CC[NH]1
C1C[NH]CCN1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CCN1
HO-
C(C)(=O)OCC
null
72
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCN(C(=O)OC(C)(C)C)CC4)cc3c2)CC1>C(C)(=O)OCC>CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCNCC4)cc3c2)CC1.Cl
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-71678daf03d8463199b3144676ffabcb
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCN(C(=O)OC(C)(C)C)CC4)cc3c2)CC1.CC(C)OS(C)(=O)=O>>CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(C(=O)OC(C)(C)C)CC2)n3C(C)C)CC1
C(C)(C)(C)OC(=O)N1CCN(CC1)C(=O)C=1NC2=CC=C(C=C2C1)OC1CCN(CC1)C(C)C.CS(=O)(=O)OC(C)C>>C(C)(C)(C)OC(=O)N1CCN(CC1)C(=O)C=1N(C2=CC=C(C=C2C1)OC1CCN(CC1)C(C)C)C(C)C
[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][cH:11][c:12]3[c:13]([cH:14]2)[cH:15][c:16]([C:17](=[O:18])[N:19]2[CH2:20][CH2:21][N:22]([C:23](=[O:24])[O:25][C:26]([CH3:27])([CH3:28])[CH3:29])[CH2:30][CH2:31]2)[nH:32]3)[CH2:36][CH2:37]1.CS(=O)(=O)O[CH:33]([CH3:34])[CH3:35]>>[CH3:1][CH:2]([CH3:3])[N:...
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCN(C(=O)OC(C)(C)C)CC4)cc3c2)CC1.CC(C)OS(C)(=O)=O
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(C(=O)OC(C)(C)C)CC2)n3C(C)C)CC1
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
d896e99f48a796a768d64b339abb5adbd8bc977c5bccdd47720d3a6657256b55
0b4f3c8c88df0a792d0db7d59004d7fe5681a61dd48ef2449ddca2d636f76ada
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
C-S(=O)(=O)-O-[CH;D3;+0:1](-[C;D1;H3:2])-[C;D1;H3:3].[C:4]-[#7:5](-[C:6](=[O;D1;H0:7])-[c:8]1:[c:9]:[c:10]:[c:11](:[c:12]):[nH;D2;+0:13]:1)-[C:14]>>[C:4]-[#7:5](-[C:6](=[O;D1;H0:7])-[c:8]1:[c:9]:[c:10]:[c:11](:[c:12]):[n;H0;D3;+0:13]:1-[CH;D3;+0:1](-[C;D1;H3:2])-[C;D1;H3:3])-[C:14]
null
[]
null
null
null
null
The title compound was prepared in analogy to example 40a), from 4-[5-(1-isopropyl-piperidin-4-yloxy)-1H-indole-2-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester and isopropyl methanesulfonate. Light-yellow foam. MS (m/z): 513.4 (M+H)+. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Mesylate
null
c1ccc2[nH]ccc2c1
c1ccc2[nH]ccc2c1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1
MsOH.HO-
null
null
null
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCN(C(=O)OC(C)(C)C)CC4)cc3c2)CC1.CC(C)OS(C)(=O)=O>>CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(C(=O)OC(C)(C)C)CC2)n3C(C)C)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-7c40ff5412994e82a0aa5a5d188694f7
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3C(C)C)CC1.CS(=O)(=O)Cl>>CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(S(C)(=O)=O)CC2)n3C(C)C)CC1
Cl.C(C)(C)N1C(=CC2=CC(=CC=C12)OC1CCN(CC1)C(C)C)C(=O)N1CCNCC1.CS(=O)(=O)Cl>>C(C)(C)N1C(=CC2=CC(=CC=C12)OC1CCN(CC1)C(C)C)C(=O)N1CCN(CC1)S(=O)(=O)C
[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][cH:11][c:12]3[c:13]([cH:14]2)[cH:15][c:16]([C:17](=[O:18])[N:19]2[CH2:20][CH2:21][NH:22][CH2:27][CH2:28]2)[n:29]3[CH:30]([CH3:31])[CH3:32])[CH2:33][CH2:34]1.Cl[S:23]([CH3:24])(=[O:25])=[O:26]>>[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]...
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3C(C)C)CC1.CS(=O)(=O)Cl
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(S(C)(=O)=O)CC2)n3C(C)C)CC1
null
null
null
Acylation
Sulfonamide synthesis (Schotten-Baumann) secondary amine
c6a995ab9be6571957febbe378833244177e30fd671e64e4e1ffe6f50345cf56
b7aca5a5d690b0846685a854bc946849e1041bfc3965161290b5ffb2821af09e
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
Cl-[S;H0;D4;+0:1](-[C;D1;H3:2])(=[O;D1;H0:3])=[O;D1;H0:4].[#7:5]1-[C:6]-[C:7]-[NH;D2;+0:8]-[C:9]-[C:10]-1>>[C;D1;H3:2]-[S;H0;D4;+0:1](=[O;D1;H0:3])(=[O;D1;H0:4])-[N;H0;D3;+0:8]1-[C:7]-[C:6]-[#7:5]-[C:10]-[C:9]-1
null
[]
null
null
null
null
The title compound was prepared in analogy to example 51, from [1-isopropyl-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-piperazin-1-yl-methanone hydrochloride and methanesulfonyl chloride. Light-yellow foam. MS (m/z): 491.2 (M+H)+. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Secondary amine.Sulfonyl halide
Tertiary amine
C1C[NH]CCN1
C1C[NH]CC[NH]1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1
HCl
null
null
null
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3C(C)C)CC1.CS(=O)(=O)Cl>>CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(S(C)(=O)=O)CC2)n3C(C)C)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3918b6de77a64d928bc11431137fefad
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCN(C(=O)OC(C)(C)C)CC4)cc3c2)CC1.O=S(=O)(OCC(F)F)C(F)(F)F>>CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(C(=O)OC(C)(C)C)CC2)n3CC(F)F)CC1
C(C)(C)(C)OC(=O)N1CCN(CC1)C(=O)C=1NC2=CC=C(C=C2C1)OC1CCN(CC1)C(C)C.FC(S(=O)(=O)OCC(F)F)(F)F>>C(C)(C)(C)OC(=O)N1CCN(CC1)C(=O)C=1N(C2=CC=C(C=C2C1)OC1CCN(CC1)C(C)C)CC(F)F
[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][cH:11][c:12]3[c:13]([cH:14]2)[cH:15][c:16]([C:17](=[O:18])[N:19]2[CH2:20][CH2:21][N:22]([C:23](=[O:24])[O:25][C:26]([CH3:27])([CH3:28])[CH3:29])[CH2:30][CH2:31]2)[nH:32]3)[CH2:37][CH2:38]1.O=S(=O)(O[CH2:33][CH:34]([F:35])[F:36])C(F)(F)F>>[CH3:1][CH:2](...
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCN(C(=O)OC(C)(C)C)CC4)cc3c2)CC1.O=S(=O)(OCC(F)F)C(F)(F)F
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(C(=O)OC(C)(C)C)CC2)n3CC(F)F)CC1
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
2385db9083aeddeec4cb75186a671c6c56d0b264d04bfd83b44fc14a91b1ba5c
edca11cebc61d00890fbfd7dabc6d5d646a584b4ea075d24940b00f620ebabf2
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
F-C(-F)(-F)-S(=O)(=O)-O-[CH2;D2;+0:1]-[C:2](-[F;D1;H0:3])-[F;D1;H0:4].[C:5]-[#7:6](-[C:7](=[O;D1;H0:8])-[c:9]1:[c:10]:[c:11]:[c:12](:[c:13]):[nH;D2;+0:14]:1)-[C:15]>>[C:5]-[#7:6](-[C:7](=[O;D1;H0:8])-[c:9]1:[c:10]:[c:11]:[c:12](:[c:13]):[n;H0;D3;+0:14]:1-[CH2;D2;+0:1]-[C:2](-[F;D1;H0:3])-[F;D1;H0:4])-[C:15]
null
[]
null
null
null
null
The title compound was prepared in analogy to example 40a), from 4-[5-(1-isopropyl-piperidin-4-yloxy)-1H-indole-2-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester and 2,2-difluoroethyl trifluoromethanesulfonate. Off-white solid. MS (m/z): 535.5 (M+H)+. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Triflate
null
c1ccc2[nH]ccc2c1
c1ccc2[nH]ccc2c1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1
TfOH.HO-
null
null
null
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCN(C(=O)OC(C)(C)C)CC4)cc3c2)CC1.O=S(=O)(OCC(F)F)C(F)(F)F>>CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(C(=O)OC(C)(C)C)CC2)n3CC(F)F)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-1040b731e88d4417a47ee661f952515d
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3CC(F)F)CC1.CS(=O)(=O)Cl>>CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(S(C)(=O)=O)CC2)n3CC(F)F)CC1
Cl.FC(CN1C(=CC2=CC(=CC=C12)OC1CCN(CC1)C(C)C)C(=O)N1CCNCC1)F.CS(=O)(=O)Cl>>FC(CN1C(=CC2=CC(=CC=C12)OC1CCN(CC1)C(C)C)C(=O)N1CCN(CC1)S(=O)(=O)C)F
[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][cH:11][c:12]3[c:13]([cH:14]2)[cH:15][c:16]([C:17](=[O:18])[N:19]2[CH2:20][CH2:21][NH:22][CH2:27][CH2:28]2)[n:29]3[CH2:30][CH:31]([F:32])[F:33])[CH2:34][CH2:35]1.Cl[S:23]([CH3:24])(=[O:25])=[O:26]>>[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][...
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3CC(F)F)CC1.CS(=O)(=O)Cl
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(S(C)(=O)=O)CC2)n3CC(F)F)CC1
null
null
null
Acylation
Sulfonamide synthesis (Schotten-Baumann) secondary amine
c6a995ab9be6571957febbe378833244177e30fd671e64e4e1ffe6f50345cf56
b7aca5a5d690b0846685a854bc946849e1041bfc3965161290b5ffb2821af09e
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
Cl-[S;H0;D4;+0:1](-[C;D1;H3:2])(=[O;D1;H0:3])=[O;D1;H0:4].[#7:5]1-[C:6]-[C:7]-[NH;D2;+0:8]-[C:9]-[C:10]-1>>[C;D1;H3:2]-[S;H0;D4;+0:1](=[O;D1;H0:3])(=[O;D1;H0:4])-[N;H0;D3;+0:8]1-[C:7]-[C:6]-[#7:5]-[C:10]-[C:9]-1
null
[]
null
null
null
null
The title compound was prepared in analogy to example 51, from [1-(2,2-difluoro-ethyl)-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-piperazin-1-yl-methanone hydrochloride and methanesulfonyl chloride. Light-yellow foam. MS (m/z): 513.4 (M+H)+. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Secondary amine.Sulfonyl halide
Tertiary amine
C1C[NH]CCN1
C1C[NH]CC[NH]1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1
HCl
null
null
null
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3CC(F)F)CC1.CS(=O)(=O)Cl>>CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(S(C)(=O)=O)CC2)n3CC(F)F)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-19388a128301464e8ee3d867e2e59cb2
CC(=O)Cl.CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3C(C)C)CC1>>CC(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)ccc3n2C(C)C)CC1
Cl.C(C)(C)N1C(=CC2=CC(=CC=C12)OC1CCN(CC1)C(C)C)C(=O)N1CCNCC1.C(C)(=O)Cl>>C(C)(C)N1C(=CC2=CC(=CC=C12)OC1CCN(CC1)C(C)C)C(=O)N1CCN(CC1)C(C)=O
Cl[C:2]([CH3:1])=[O:3].[NH:4]1[CH2:5][CH2:6][N:7]([C:8](=[O:9])[c:10]2[cH:11][c:12]3[cH:13][c:14]([O:15][CH:16]4[CH2:17][CH2:18][N:19]([CH:20]([CH3:21])[CH3:22])[CH2:23][CH2:24]4)[cH:25][cH:26][c:27]3[n:28]2[CH:29]([CH3:30])[CH3:31])[CH2:32][CH2:33]1>>[CH3:1][C:2](=[O:3])[N:4]1[CH2:5][CH2:6][N:7]([C:8](=[O:9])[c:10]2[c...
CC(=O)Cl.CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3C(C)C)CC1
CC(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)ccc3n2C(C)C)CC1
null
null
null
Acylation
N-alkylation of secondary amines with alkyl halides
6dd420fad17fb719b6bd840e8952a8d7b2fb24721f86f8b8f9c697a36eb97ec3
96cb0a2fed10552c5770a45a2d6523b47ac3e38928b4a9c698d8577451182dcd
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
Cl-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3].[#7:4]1-[C:5]-[C:6]-[NH;D2;+0:7]-[C:8]-[C:9]-1>>[C;D1;H3:2]-[C;H0;D3;+0:1](=[O;D1;H0:3])-[N;H0;D3;+0:7]1-[C:6]-[C:5]-[#7:4]-[C:9]-[C:8]-1
null
[]
null
null
null
null
The title compound was prepared in analogy to example 51, from [1-isopropyl-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-piperazin-1-yl-methanone hydrochloride and acetyl chloride. Light-yellow foam. MS (m/z): 455.5 (M+H)+. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Secondary amine
Tertiary amide
C1CNCC[NH]1
C1C[NH]CC[NH]1
C1C[NH]CC[NH]1.c1ccc2[nH]ccc2c1.C1CC[NH]CC1
HCl
null
null
null
CC(=O)Cl.CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3C(C)C)CC1>>CC(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)ccc3n2C(C)C)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-c0ac151c3c9346e78b992cda606a1a94
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCNCC4)cc3c2)CC1.O=S(=O)(Cl)CC(F)(F)F>>CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCN(S(=O)(=O)CC(F)(F)F)CC4)cc3c2)CC1
Cl.Cl.C(C)(C)N1CCC(CC1)OC=1C=C2C=C(NC2=CC1)C(=O)N1CCNCC1.FC(CS(=O)(=O)Cl)(F)F>>C(C)(C)N1CCC(CC1)OC=1C=C2C=C(NC2=CC1)C(=O)N1CCN(CC1)S(=O)(=O)CC(F)(F)F
[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][cH:11][c:12]3[nH:13][c:14]([C:15](=[O:16])[N:17]4[CH2:18][CH2:19][NH:20][CH2:29][CH2:30]4)[cH:31][c:32]3[cH:33]2)[CH2:34][CH2:35]1.Cl[S:21](=[O:22])(=[O:23])[CH2:24][C:25]([F:26])([F:27])[F:28]>>[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:...
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCNCC4)cc3c2)CC1.O=S(=O)(Cl)CC(F)(F)F
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCN(S(=O)(=O)CC(F)(F)F)CC4)cc3c2)CC1
null
null
null
Acylation
Sulfonamide synthesis (Schotten-Baumann) secondary amine
c6a995ab9be6571957febbe378833244177e30fd671e64e4e1ffe6f50345cf56
b7aca5a5d690b0846685a854bc946849e1041bfc3965161290b5ffb2821af09e
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
Cl-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[C:4]-[C:5](-[F;D1;H0:6])(-[F;D1;H0:7])-[F;D1;H0:8].[#7:9]1-[C:10]-[C:11]-[NH;D2;+0:12]-[C:13]-[C:14]-1>>[F;D1;H0:6]-[C:5](-[F;D1;H0:7])(-[F;D1;H0:8])-[C:4]-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[N;H0;D3;+0:12]1-[C:11]-[C:10]-[#7:9]-[C:14]-[C:13]-1
null
[]
null
null
null
null
The title compound was prepared in analogy to example 51, from [5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-piperazin-1-yl-methanone dihydrochloride and 2,2,2-trifluoro-ethanesulfonyl chloride. Off-white solid. MS (m/z): 517.3 (M+H)+. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Secondary amine.Sulfonyl halide
Tertiary amine
C1C[NH]CCN1
C1C[NH]CC[NH]1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1
HCl
null
null
null
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCNCC4)cc3c2)CC1.O=S(=O)(Cl)CC(F)(F)F>>CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCN(S(=O)(=O)CC(F)(F)F)CC4)cc3c2)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-382105d56dcf4436bc52eca81bd4e6b4
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCNCC4)cc3c2)CC1.O=C(Cl)C1CC1>>CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCN(C(=O)C5CC5)CC4)cc3c2)CC1
Cl.Cl.C(C)(C)N1CCC(CC1)OC=1C=C2C=C(NC2=CC1)C(=O)N1CCNCC1.C1(CC1)C(=O)Cl>>C1(CC1)C(=O)N1CCN(CC1)C(=O)C=1NC2=CC=C(C=C2C1)OC1CCN(CC1)C(C)C
[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][cH:11][c:12]3[nH:13][c:14]([C:15](=[O:16])[N:17]4[CH2:18][CH2:19][NH:20][CH2:26][CH2:27]4)[cH:28][c:29]3[cH:30]2)[CH2:31][CH2:32]1.Cl[C:21](=[O:22])[CH:23]1[CH2:24][CH2:25]1>>[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][cH:11][c:...
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCNCC4)cc3c2)CC1.O=C(Cl)C1CC1
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCN(C(=O)C5CC5)CC4)cc3c2)CC1
null
null
null
Acylation
N-alkylation of secondary amines with alkyl halides
008ee4368afbd52034630a2410a1738f53049b314574435184e4e0be81b96642
96cb0a2fed10552c5770a45a2d6523b47ac3e38928b4a9c698d8577451182dcd
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCN(C(=O)C2CC2)CC1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]1-[C:4]-[C:5]-1.[#7:6]1-[C:7]-[C:8]-[NH;D2;+0:9]-[C:10]-[C:11]-1>>[O;D1;H0:2]=[C;H0;D3;+0:1](-[C:3]1-[C:4]-[C:5]-1)-[N;H0;D3;+0:9]1-[C:8]-[C:7]-[#7:6]-[C:11]-[C:10]-1
null
[]
null
null
null
null
The title compound was prepared in analogy to example 51, from [5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-piperazin-1-yl-methanone dihydrochloride and cyclopropanoyl chloride. Light-yellow solid. MS (m/z): 439.5 (M+H)+. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Secondary amine
Tertiary amide
C1C[NH]CCN1
C1C[NH]CC[NH]1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1.C1CC1
HCl
null
null
null
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCNCC4)cc3c2)CC1.O=C(Cl)C1CC1>>CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCN(C(=O)C5CC5)CC4)cc3c2)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-87f57e94d60c439abf48c98e8adc4d43
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCNCC4)cc3c2)CC1.COC(=O)Cl>>COC(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)ccc3[nH]2)CC1
Cl.Cl.C(C)(C)N1CCC(CC1)OC=1C=C2C=C(NC2=CC1)C(=O)N1CCNCC1.ClC(=O)OC>>COC(=O)N1CCN(CC1)C(=O)C=1NC2=CC=C(C=C2C1)OC1CCN(CC1)C(C)C
[NH:5]1[CH2:6][CH2:7][N:8]([C:9](=[O:10])[c:11]2[cH:12][c:13]3[cH:14][c:15]([O:16][CH:17]4[CH2:18][CH2:19][N:20]([CH:21]([CH3:22])[CH3:23])[CH2:24][CH2:25]4)[cH:26][cH:27][c:28]3[nH:29]2)[CH2:30][CH2:31]1.Cl[C:3]([O:2][CH3:1])=[O:4]>>[CH3:1][O:2][C:3](=[O:4])[N:5]1[CH2:6][CH2:7][N:8]([C:9](=[O:10])[c:11]2[cH:12][c:13]3...
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCNCC4)cc3c2)CC1.COC(=O)Cl
COC(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)ccc3[nH]2)CC1
null
null
null
Protection
N-alkylation of secondary amines with alkyl halides
98754a5b02829fe15e66bc7afa63abfcc67bc327dedcd37a6b6b54543d6e3170
d86dc1e6d0e089b3444b62ddfcf4c4822bdac4b60e628553036562518c29adcd
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#8:3]-[C;D1;H3:4].[#7:5]1-[C:6]-[C:7]-[NH;D2;+0:8]-[C:9]-[C:10]-1>>[C;D1;H3:4]-[#8:3]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[N;H0;D3;+0:8]1-[C:7]-[C:6]-[#7:5]-[C:10]-[C:9]-1
null
[]
null
null
null
null
The title compound was prepared in analogy to example 51, from [5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-piperazin-1-yl-methanone dihydrochloride and methyl chloroformate. Light-yellow solid. MS (m/z): 429.3 (M+H)+. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Ether.Secondary amine
Carbamic ester
C1CNCC[NH]1
C1C[NH]CC[NH]1
C1C[NH]CC[NH]1.c1ccc2[nH]ccc2c1.C1CC[NH]CC1
HCl
null
null
null
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCNCC4)cc3c2)CC1.COC(=O)Cl>>COC(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)ccc3[nH]2)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-f7af323561ac40bd8dbd777457b6dda2
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCNCC4)cc3c2)CC1.CN(C)C(=O)Cl>>CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCN(C(=O)N(C)C)CC4)cc3c2)CC1
Cl.Cl.C(C)(C)N1CCC(CC1)OC=1C=C2C=C(NC2=CC1)C(=O)N1CCNCC1.CN(C(=O)Cl)C>>CN(C(=O)N1CCN(CC1)C(=O)C=1NC2=CC=C(C=C2C1)OC1CCN(CC1)C(C)C)C
[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][cH:11][c:12]3[nH:13][c:14]([C:15](=[O:16])[N:17]4[CH2:18][CH2:19][NH:20][CH2:26][CH2:27]4)[cH:28][c:29]3[cH:30]2)[CH2:31][CH2:32]1.Cl[C:21](=[O:22])[N:23]([CH3:24])[CH3:25]>>[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][cH:11][c:1...
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCNCC4)cc3c2)CC1.CN(C)C(=O)Cl
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCN(C(=O)N(C)C)CC4)cc3c2)CC1
null
null
null
Acylation
N-alkylation of secondary amines with alkyl halides
dcfba2aa7ca13a6ccdf0aa9e5554d01dee20f5aad8e3132e302a663220e425bb
353c6e1db25433862a8bcf26ca332f6abeb45cb685806584bc65f8cfcb712540
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#7:3](-[C;D1;H3:4])-[C;D1;H3:5].[#7:6]1-[C:7]-[C:8]-[NH;D2;+0:9]-[C:10]-[C:11]-1>>[C;D1;H3:4]-[#7:3](-[C;D1;H3:5])-[C;H0;D3;+0:1](=[O;D1;H0:2])-[N;H0;D3;+0:9]1-[C:8]-[C:7]-[#7:6]-[C:11]-[C:10]-1
null
[]
null
null
null
null
The title compound was prepared in analogy to example 51, from [5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-piperazin-1-yl-methanone dihydrochloride and N,N-dimethylcarbamoyl chloride. Off-white solid. MS (m/z): 442.3 (M+H)+. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Tertiary amide.Secondary amine
Urea
C1C[NH]CCN1
C1C[NH]CC[NH]1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1
HCl
null
null
null
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCNCC4)cc3c2)CC1.CN(C)C(=O)Cl>>CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCN(C(=O)N(C)C)CC4)cc3c2)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-bb9d5cfda14c4a06994d7933fceb2b78
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCNCC4)cc3c2)CC1.CCN(CC)C(=O)Cl>>CCN(CC)C(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)ccc3[nH]2)CC1
Cl.Cl.C(C)(C)N1CCC(CC1)OC=1C=C2C=C(NC2=CC1)C(=O)N1CCNCC1.C(C)N(C(=O)Cl)CC>>C(C)N(C(=O)N1CCN(CC1)C(=O)C=1NC2=CC=C(C=C2C1)OC1CCN(CC1)C(C)C)CC
[NH:8]1[CH2:9][CH2:10][N:11]([C:12](=[O:13])[c:14]2[cH:15][c:16]3[cH:17][c:18]([O:19][CH:20]4[CH2:21][CH2:22][N:23]([CH:24]([CH3:25])[CH3:26])[CH2:27][CH2:28]4)[cH:29][cH:30][c:31]3[nH:32]2)[CH2:33][CH2:34]1.Cl[C:6]([N:3]([CH2:2][CH3:1])[CH2:4][CH3:5])=[O:7]>>[CH3:1][CH2:2][N:3]([CH2:4][CH3:5])[C:6](=[O:7])[N:8]1[CH2:9...
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCNCC4)cc3c2)CC1.CCN(CC)C(=O)Cl
CCN(CC)C(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)ccc3[nH]2)CC1
null
null
null
Acylation
N-alkylation of secondary amines with alkyl halides
9f480cf7d56f704fd9b7f19410e93a0b335ca09273ad87dbe310c5462f719bdc
353c6e1db25433862a8bcf26ca332f6abeb45cb685806584bc65f8cfcb712540
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#7:3](-[C:4])-[C:5].[#7:6]1-[C:7]-[C:8]-[NH;D2;+0:9]-[C:10]-[C:11]-1>>[C:4]-[#7:3](-[C:5])-[C;H0;D3;+0:1](=[O;D1;H0:2])-[N;H0;D3;+0:9]1-[C:10]-[C:11]-[#7:6]-[C:7]-[C:8]-1
null
[]
null
null
null
null
The title compound was prepared in analogy to example 51, from [5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-piperazin-1-yl-methanone dihydrochloride and N,N-diethylcarbamoyl chloride. Off-white solid. MS (m/z): 470.6 (M+H)+. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Tertiary amide.Secondary amine
Urea
C1CNCC[NH]1
C1C[NH]CC[NH]1
C1C[NH]CC[NH]1.c1ccc2[nH]ccc2c1.C1CC[NH]CC1
HCl
null
null
null
CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCNCC4)cc3c2)CC1.CCN(CC)C(=O)Cl>>CCN(CC)C(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)ccc3[nH]2)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-cfb1338ead364847928af1d93d45ec38
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3CC(F)F)CC1.CC(C)S(=O)(=O)Cl>>CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(S(=O)(=O)C(C)C)CC2)n3CC(F)F)CC1
Cl.FC(CN1C(=CC2=CC(=CC=C12)OC1CCN(CC1)C(C)C)C(=O)N1CCNCC1)F.CC(C)S(=O)(=O)Cl>>FC(CN1C(=CC2=CC(=CC=C12)OC1CCN(CC1)C(C)C)C(=O)N1CCN(CC1)S(=O)(=O)C(C)C)F
[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][cH:11][c:12]3[c:13]([cH:14]2)[cH:15][c:16]([C:17](=[O:18])[N:19]2[CH2:20][CH2:21][NH:22][CH2:29][CH2:30]2)[n:31]3[CH2:32][CH:33]([F:34])[F:35])[CH2:36][CH2:37]1.Cl[S:23](=[O:24])(=[O:25])[CH:26]([CH3:27])[CH3:28]>>[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH...
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3CC(F)F)CC1.CC(C)S(=O)(=O)Cl
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(S(=O)(=O)C(C)C)CC2)n3CC(F)F)CC1
null
null
null
Acylation
Sulfonamide synthesis (Schotten-Baumann) secondary amine
c6a995ab9be6571957febbe378833244177e30fd671e64e4e1ffe6f50345cf56
b7aca5a5d690b0846685a854bc946849e1041bfc3965161290b5ffb2821af09e
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
Cl-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[C:4](-[C;D1;H3:5])-[C;D1;H3:6].[#7:7]1-[C:8]-[C:9]-[NH;D2;+0:10]-[C:11]-[C:12]-1>>[C;D1;H3:5]-[C:4](-[C;D1;H3:6])-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[N;H0;D3;+0:10]1-[C:9]-[C:8]-[#7:7]-[C:12]-[C:11]-1
null
[]
null
null
null
null
The title compound was prepared in analogy to example 51, from [1-(2,2-difluoro-ethyl)-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-piperazin-1-yl-methanone hydrochloride and 2-propanesulfonyl chloride. Light-yellow solid. MS (m/z): 541.3 (M+H)+. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Secondary amine.Sulfonyl halide
Tertiary amine
C1C[NH]CCN1
C1C[NH]CC[NH]1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1
HCl
null
null
null
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3CC(F)F)CC1.CC(C)S(=O)(=O)Cl>>CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(S(=O)(=O)C(C)C)CC2)n3CC(F)F)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ed6980d1808a40398d906655820e2cf6
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3CC(F)F)CC1.O=C(Cl)C1CC1>>CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(C(=O)C4CC4)CC2)n3CC(F)F)CC1
Cl.FC(CN1C(=CC2=CC(=CC=C12)OC1CCN(CC1)C(C)C)C(=O)N1CCNCC1)F.C1(CC1)C(=O)Cl>>C1(CC1)C(=O)N1CCN(CC1)C(=O)C=1N(C2=CC=C(C=C2C1)OC1CCN(CC1)C(C)C)CC(F)F
[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][cH:11][c:12]3[c:13]([cH:14]2)[cH:15][c:16]([C:17](=[O:18])[N:19]2[CH2:20][CH2:21][NH:22][CH2:28][CH2:29]2)[n:30]3[CH2:31][CH:32]([F:33])[F:34])[CH2:35][CH2:36]1.Cl[C:23](=[O:24])[CH:25]1[CH2:26][CH2:27]1>>[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7...
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3CC(F)F)CC1.O=C(Cl)C1CC1
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(C(=O)C4CC4)CC2)n3CC(F)F)CC1
null
null
null
Acylation
N-alkylation of secondary amines with alkyl halides
008ee4368afbd52034630a2410a1738f53049b314574435184e4e0be81b96642
96cb0a2fed10552c5770a45a2d6523b47ac3e38928b4a9c698d8577451182dcd
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCN(C(=O)C2CC2)CC1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]1-[C:4]-[C:5]-1.[#7:6]1-[C:7]-[C:8]-[NH;D2;+0:9]-[C:10]-[C:11]-1>>[O;D1;H0:2]=[C;H0;D3;+0:1](-[C:3]1-[C:4]-[C:5]-1)-[N;H0;D3;+0:9]1-[C:8]-[C:7]-[#7:6]-[C:11]-[C:10]-1
null
[]
null
null
null
null
The title compound was prepared in analogy to example 51, from [1-(2,2-difluoro-ethyl)-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-piperazin-1-yl-methanone hydrochloride and cyclopropanoyl chloride. Off-white solid. MS (m/z): 503.2 (M+H)+. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Secondary amine
Tertiary amide
C1C[NH]CCN1
C1C[NH]CC[NH]1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1.C1CC1
HCl
null
null
null
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3CC(F)F)CC1.O=C(Cl)C1CC1>>CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(C(=O)C4CC4)CC2)n3CC(F)F)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-7d9c0a156feb4065a98cadd44a99b88a
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3CC(F)F)CC1.O=S(=O)(Cl)CC(F)(F)F>>CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(S(=O)(=O)CC(F)(F)F)CC2)n3CC(F)F)CC1
Cl.FC(CN1C(=CC2=CC(=CC=C12)OC1CCN(CC1)C(C)C)C(=O)N1CCNCC1)F.FC(CS(=O)(=O)Cl)(F)F>>FC(CN1C(=CC2=CC(=CC=C12)OC1CCN(CC1)C(C)C)C(=O)N1CCN(CC1)S(=O)(=O)CC(F)(F)F)F
[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][cH:11][c:12]3[c:13]([cH:14]2)[cH:15][c:16]([C:17](=[O:18])[N:19]2[CH2:20][CH2:21][NH:22][CH2:31][CH2:32]2)[n:33]3[CH2:34][CH:35]([F:36])[F:37])[CH2:38][CH2:39]1.Cl[S:23](=[O:24])(=[O:25])[CH2:26][C:27]([F:28])([F:29])[F:30]>>[CH3:1][CH:2]([CH3:3])[N:4]...
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3CC(F)F)CC1.O=S(=O)(Cl)CC(F)(F)F
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(S(=O)(=O)CC(F)(F)F)CC2)n3CC(F)F)CC1
null
null
null
Acylation
Sulfonamide synthesis (Schotten-Baumann) secondary amine
c6a995ab9be6571957febbe378833244177e30fd671e64e4e1ffe6f50345cf56
b7aca5a5d690b0846685a854bc946849e1041bfc3965161290b5ffb2821af09e
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
Cl-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[C:4]-[C:5](-[F;D1;H0:6])(-[F;D1;H0:7])-[F;D1;H0:8].[#7:9]1-[C:10]-[C:11]-[NH;D2;+0:12]-[C:13]-[C:14]-1>>[F;D1;H0:6]-[C:5](-[F;D1;H0:7])(-[F;D1;H0:8])-[C:4]-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[N;H0;D3;+0:12]1-[C:11]-[C:10]-[#7:9]-[C:14]-[C:13]-1
null
[]
null
null
null
null
The title compound was prepared in analogy to example 51, from [1-(2,2-difluoro-ethyl)-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-piperazin-1-yl-methanone hydrochloride and 2,2,2-trifluoro-ethanesulfonyl chloride. Light-yellow solid. MS (m/z): 581.3 (M+H)+. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Secondary amine.Sulfonyl halide
Tertiary amine
C1C[NH]CCN1
C1C[NH]CC[NH]1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1
HCl
null
null
null
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3CC(F)F)CC1.O=S(=O)(Cl)CC(F)(F)F>>CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(S(=O)(=O)CC(F)(F)F)CC2)n3CC(F)F)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-e7b6fac5fd3942649843ebfb88f09278
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3CC(F)F)CC1.COC(=O)Cl>>COC(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)ccc3n2CC(F)F)CC1
Cl.FC(CN1C(=CC2=CC(=CC=C12)OC1CCN(CC1)C(C)C)C(=O)N1CCNCC1)F.ClC(=O)OC>>COC(=O)N1CCN(CC1)C(=O)C=1N(C2=CC=C(C=C2C1)OC1CCN(CC1)C(C)C)CC(F)F
[NH:5]1[CH2:6][CH2:7][N:8]([C:9](=[O:10])[c:11]2[cH:12][c:13]3[cH:14][c:15]([O:16][CH:17]4[CH2:18][CH2:19][N:20]([CH:21]([CH3:22])[CH3:23])[CH2:24][CH2:25]4)[cH:26][cH:27][c:28]3[n:29]2[CH2:30][CH:31]([F:32])[F:33])[CH2:34][CH2:35]1.Cl[C:3]([O:2][CH3:1])=[O:4]>>[CH3:1][O:2][C:3](=[O:4])[N:5]1[CH2:6][CH2:7][N:8]([C:9](=...
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3CC(F)F)CC1.COC(=O)Cl
COC(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)ccc3n2CC(F)F)CC1
null
null
null
Protection
N-alkylation of secondary amines with alkyl halides
98754a5b02829fe15e66bc7afa63abfcc67bc327dedcd37a6b6b54543d6e3170
d86dc1e6d0e089b3444b62ddfcf4c4822bdac4b60e628553036562518c29adcd
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#8:3]-[C;D1;H3:4].[#7:5]1-[C:6]-[C:7]-[NH;D2;+0:8]-[C:9]-[C:10]-1>>[C;D1;H3:4]-[#8:3]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[N;H0;D3;+0:8]1-[C:7]-[C:6]-[#7:5]-[C:10]-[C:9]-1
null
[]
null
null
null
null
The title compound was prepared in analogy to example 51, from [1-(2,2-difluoro-ethyl)-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-piperazin-1-yl-methanone hydrochloride and methyl chloroformate. Light-yellow solid. MS (m/z): 493.2 (M+H)+. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Ether.Secondary amine
Carbamic ester
C1CNCC[NH]1
C1C[NH]CC[NH]1
C1C[NH]CC[NH]1.c1ccc2[nH]ccc2c1.C1CC[NH]CC1
HCl
null
null
null
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3CC(F)F)CC1.COC(=O)Cl>>COC(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)ccc3n2CC(F)F)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-4b36ce3541724bef9408a57b3288fb20
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3CC(F)F)CC1.CN(C)C(=O)Cl>>CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(C(=O)N(C)C)CC2)n3CC(F)F)CC1
Cl.FC(CN1C(=CC2=CC(=CC=C12)OC1CCN(CC1)C(C)C)C(=O)N1CCNCC1)F.CN(C(=O)Cl)C>>CN(C(=O)N1CCN(CC1)C(=O)C=1N(C2=CC=C(C=C2C1)OC1CCN(CC1)C(C)C)CC(F)F)C
[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][cH:11][c:12]3[c:13]([cH:14]2)[cH:15][c:16]([C:17](=[O:18])[N:19]2[CH2:20][CH2:21][NH:22][CH2:28][CH2:29]2)[n:30]3[CH2:31][CH:32]([F:33])[F:34])[CH2:35][CH2:36]1.Cl[C:23](=[O:24])[N:25]([CH3:26])[CH3:27]>>[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]...
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3CC(F)F)CC1.CN(C)C(=O)Cl
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(C(=O)N(C)C)CC2)n3CC(F)F)CC1
null
null
null
Acylation
N-alkylation of secondary amines with alkyl halides
dcfba2aa7ca13a6ccdf0aa9e5554d01dee20f5aad8e3132e302a663220e425bb
353c6e1db25433862a8bcf26ca332f6abeb45cb685806584bc65f8cfcb712540
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#7:3](-[C;D1;H3:4])-[C;D1;H3:5].[#7:6]1-[C:7]-[C:8]-[NH;D2;+0:9]-[C:10]-[C:11]-1>>[C;D1;H3:4]-[#7:3](-[C;D1;H3:5])-[C;H0;D3;+0:1](=[O;D1;H0:2])-[N;H0;D3;+0:9]1-[C:8]-[C:7]-[#7:6]-[C:11]-[C:10]-1
null
[]
null
null
null
null
The title compound was prepared in analogy to example 51, from [1-(2,2-difluoro-ethyl)-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-piperazin-1-yl-methanone hydrochloride and N,N-dimethylcarbamoyl chloride. Off-white solid. MS (m/z): 506.4 (M+H)+. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Tertiary amide.Secondary amine
Urea
C1C[NH]CCN1
C1C[NH]CC[NH]1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1
HCl
null
null
null
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3CC(F)F)CC1.CN(C)C(=O)Cl>>CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(C(=O)N(C)C)CC2)n3CC(F)F)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-404c8fffa7124c2dbf7089c2aded08e2
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3CC(F)F)CC1.CCN(CC)C(=O)Cl>>CCN(CC)C(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)ccc3n2CC(F)F)CC1
Cl.FC(CN1C(=CC2=CC(=CC=C12)OC1CCN(CC1)C(C)C)C(=O)N1CCNCC1)F.C(C)N(C(=O)Cl)CC>>C(C)N(C(=O)N1CCN(CC1)C(=O)C=1N(C2=CC=C(C=C2C1)OC1CCN(CC1)C(C)C)CC(F)F)CC
[NH:8]1[CH2:9][CH2:10][N:11]([C:12](=[O:13])[c:14]2[cH:15][c:16]3[cH:17][c:18]([O:19][CH:20]4[CH2:21][CH2:22][N:23]([CH:24]([CH3:25])[CH3:26])[CH2:27][CH2:28]4)[cH:29][cH:30][c:31]3[n:32]2[CH2:33][CH:34]([F:35])[F:36])[CH2:37][CH2:38]1.Cl[C:6]([N:3]([CH2:2][CH3:1])[CH2:4][CH3:5])=[O:7]>>[CH3:1][CH2:2][N:3]([CH2:4][CH3:...
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3CC(F)F)CC1.CCN(CC)C(=O)Cl
CCN(CC)C(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)ccc3n2CC(F)F)CC1
null
null
null
Acylation
N-alkylation of secondary amines with alkyl halides
9f480cf7d56f704fd9b7f19410e93a0b335ca09273ad87dbe310c5462f719bdc
353c6e1db25433862a8bcf26ca332f6abeb45cb685806584bc65f8cfcb712540
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#7:3](-[C:4])-[C:5].[#7:6]1-[C:7]-[C:8]-[NH;D2;+0:9]-[C:10]-[C:11]-1>>[C:4]-[#7:3](-[C:5])-[C;H0;D3;+0:1](=[O;D1;H0:2])-[N;H0;D3;+0:9]1-[C:10]-[C:11]-[#7:6]-[C:7]-[C:8]-1
null
[]
null
null
null
null
The title compound was prepared in analogy to example 51, from [1-(2,2-difluoro-ethyl)-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-piperazin-1-yl-methanone hydrochloride and N,N-diethylcarbamoyl chloride. Off-white solid. MS (m/z): 534.3 (M+H)+. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Tertiary amide.Secondary amine
Urea
C1CNCC[NH]1
C1C[NH]CC[NH]1
C1C[NH]CC[NH]1.c1ccc2[nH]ccc2c1.C1CC[NH]CC1
HCl
null
null
null
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3CC(F)F)CC1.CCN(CC)C(=O)Cl>>CCN(CC)C(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)ccc3n2CC(F)F)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3159aa5af3f9439fad1f68b2b64e444b
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3CC(F)F)CC1.CN(C)S(=O)(=O)Cl>>CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(S(=O)(=O)N(C)C)CC2)n3CC(F)F)CC1
Cl.FC(CN1C(=CC2=CC(=CC=C12)OC1CCN(CC1)C(C)C)C(=O)N1CCNCC1)F.CN(S(=O)(=O)Cl)C>>CN(S(=O)(=O)N1CCN(CC1)C(=O)C=1N(C2=CC=C(C=C2C1)OC1CCN(CC1)C(C)C)CC(F)F)C
[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][cH:11][c:12]3[c:13]([cH:14]2)[cH:15][c:16]([C:17](=[O:18])[N:19]2[CH2:20][CH2:21][NH:22][CH2:29][CH2:30]2)[n:31]3[CH2:32][CH:33]([F:34])[F:35])[CH2:36][CH2:37]1.Cl[S:23](=[O:24])(=[O:25])[N:26]([CH3:27])[CH3:28]>>[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2...
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3CC(F)F)CC1.CN(C)S(=O)(=O)Cl
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(S(=O)(=O)N(C)C)CC2)n3CC(F)F)CC1
null
null
null
Acylation
Sulfonamide synthesis (Schotten-Baumann) secondary amine
9472b3d472badfbf976c26bebba6611bda86b371cf2a2283d41c5954a87661db
6c2a4c35ccae10843ff928afe56a8d3bc92b152c9bcc4d800e2ad816b6c86d86
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
Cl-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[#7:4](-[C;D1;H3:5])-[C;D1;H3:6].[#7:7]1-[C:8]-[C:9]-[NH;D2;+0:10]-[C:11]-[C:12]-1>>[C;D1;H3:5]-[#7:4](-[C;D1;H3:6])-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[N;H0;D3;+0:10]1-[C:9]-[C:8]-[#7:7]-[C:12]-[C:11]-1
null
[]
null
null
null
null
The title compound was prepared in analogy to example 51, from [1-(2,2-difluoro-ethyl)-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-piperazin-1-yl-methanone hydrochloride and dimethylsulfamoyl chloride. Light-yellow solid. MS (m/z): 542.3 (M+H)+. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Secondary amine
Tertiary amine
C1C[NH]CCN1
C1C[NH]CC[NH]1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1
HCl
null
null
null
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3CC(F)F)CC1.CN(C)S(=O)(=O)Cl>>CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(S(=O)(=O)N(C)C)CC2)n3CC(F)F)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-5120230619c8480f96c7be153d77ec80
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3C(C)C)CC1.CC(C)S(=O)(=O)Cl>>CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(S(=O)(=O)C(C)C)CC2)n3C(C)C)CC1
Cl.C(C)(C)N1C(=CC2=CC(=CC=C12)OC1CCN(CC1)C(C)C)C(=O)N1CCNCC1.CC(C)S(=O)(=O)Cl>>C(C)(C)N1C(=CC2=CC(=CC=C12)OC1CCN(CC1)C(C)C)C(=O)N1CCN(CC1)S(=O)(=O)C(C)C
[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][cH:11][c:12]3[c:13]([cH:14]2)[cH:15][c:16]([C:17](=[O:18])[N:19]2[CH2:20][CH2:21][NH:22][CH2:29][CH2:30]2)[n:31]3[CH:32]([CH3:33])[CH3:34])[CH2:35][CH2:36]1.Cl[S:23](=[O:24])(=[O:25])[CH:26]([CH3:27])[CH3:28]>>[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6]...
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3C(C)C)CC1.CC(C)S(=O)(=O)Cl
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(S(=O)(=O)C(C)C)CC2)n3C(C)C)CC1
null
null
null
Acylation
Sulfonamide synthesis (Schotten-Baumann) secondary amine
c6a995ab9be6571957febbe378833244177e30fd671e64e4e1ffe6f50345cf56
b7aca5a5d690b0846685a854bc946849e1041bfc3965161290b5ffb2821af09e
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
Cl-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[C:4](-[C;D1;H3:5])-[C;D1;H3:6].[#7:7]1-[C:8]-[C:9]-[NH;D2;+0:10]-[C:11]-[C:12]-1>>[C;D1;H3:5]-[C:4](-[C;D1;H3:6])-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[N;H0;D3;+0:10]1-[C:9]-[C:8]-[#7:7]-[C:12]-[C:11]-1
null
[]
null
null
null
null
The title compound was prepared in analogy to example 51, from [1-isopropyl-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-piperazin-1-yl-methanone hydrochloride and 2-propanesulfonyl chloride. Off-white solid. MS (m/z): 519.3 (M+H)+. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Secondary amine.Sulfonyl halide
Tertiary amine
C1C[NH]CCN1
C1C[NH]CC[NH]1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1
HCl
null
null
null
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3C(C)C)CC1.CC(C)S(=O)(=O)Cl>>CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(S(=O)(=O)C(C)C)CC2)n3C(C)C)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-eb1cc6f7607f4d44ac6677ec2084b722
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3C(C)C)CC1.O=C(Cl)C1CC1>>CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(C(=O)C4CC4)CC2)n3C(C)C)CC1
Cl.C(C)(C)N1C(=CC2=CC(=CC=C12)OC1CCN(CC1)C(C)C)C(=O)N1CCNCC1.C1(CC1)C(=O)Cl>>C1(CC1)C(=O)N1CCN(CC1)C(=O)C=1N(C2=CC=C(C=C2C1)OC1CCN(CC1)C(C)C)C(C)C
[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][cH:11][c:12]3[c:13]([cH:14]2)[cH:15][c:16]([C:17](=[O:18])[N:19]2[CH2:20][CH2:21][NH:22][CH2:28][CH2:29]2)[n:30]3[CH:31]([CH3:32])[CH3:33])[CH2:34][CH2:35]1.Cl[C:23](=[O:24])[CH:25]1[CH2:26][CH2:27]1>>[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O...
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3C(C)C)CC1.O=C(Cl)C1CC1
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(C(=O)C4CC4)CC2)n3C(C)C)CC1
null
null
null
Acylation
N-alkylation of secondary amines with alkyl halides
008ee4368afbd52034630a2410a1738f53049b314574435184e4e0be81b96642
96cb0a2fed10552c5770a45a2d6523b47ac3e38928b4a9c698d8577451182dcd
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCN(C(=O)C2CC2)CC1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]1-[C:4]-[C:5]-1.[#7:6]1-[C:7]-[C:8]-[NH;D2;+0:9]-[C:10]-[C:11]-1>>[O;D1;H0:2]=[C;H0;D3;+0:1](-[C:3]1-[C:4]-[C:5]-1)-[N;H0;D3;+0:9]1-[C:8]-[C:7]-[#7:6]-[C:11]-[C:10]-1
null
[]
null
null
null
null
The title compound was prepared in analogy to example 51, from [1-isopropyl-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-piperazin-1-yl-methanone hydrochloride and cyclopropanoyl chloride. Light-yellow solid. MS (m/z): 481.5 (M+H)+. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Secondary amine
Tertiary amide
C1C[NH]CCN1
C1C[NH]CC[NH]1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1.C1CC1
HCl
null
null
null
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3C(C)C)CC1.O=C(Cl)C1CC1>>CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(C(=O)C4CC4)CC2)n3C(C)C)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-5dd32515a0e04f91ae30da32c08171de
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3C(C)C)CC1.O=S(=O)(Cl)CC(F)(F)F>>CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(S(=O)(=O)CC(F)(F)F)CC2)n3C(C)C)CC1
Cl.C(C)(C)N1C(=CC2=CC(=CC=C12)OC1CCN(CC1)C(C)C)C(=O)N1CCNCC1.FC(CS(=O)(=O)Cl)(F)F>>C(C)(C)N1C(=CC2=CC(=CC=C12)OC1CCN(CC1)C(C)C)C(=O)N1CCN(CC1)S(=O)(=O)CC(F)(F)F
[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][cH:11][c:12]3[c:13]([cH:14]2)[cH:15][c:16]([C:17](=[O:18])[N:19]2[CH2:20][CH2:21][NH:22][CH2:31][CH2:32]2)[n:33]3[CH:34]([CH3:35])[CH3:36])[CH2:37][CH2:38]1.Cl[S:23](=[O:24])(=[O:25])[CH2:26][C:27]([F:28])([F:29])[F:30]>>[CH3:1][CH:2]([CH3:3])[N:4]1[CH...
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3C(C)C)CC1.O=S(=O)(Cl)CC(F)(F)F
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(S(=O)(=O)CC(F)(F)F)CC2)n3C(C)C)CC1
null
null
null
Acylation
Sulfonamide synthesis (Schotten-Baumann) secondary amine
c6a995ab9be6571957febbe378833244177e30fd671e64e4e1ffe6f50345cf56
b7aca5a5d690b0846685a854bc946849e1041bfc3965161290b5ffb2821af09e
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
Cl-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[C:4]-[C:5](-[F;D1;H0:6])(-[F;D1;H0:7])-[F;D1;H0:8].[#7:9]1-[C:10]-[C:11]-[NH;D2;+0:12]-[C:13]-[C:14]-1>>[F;D1;H0:6]-[C:5](-[F;D1;H0:7])(-[F;D1;H0:8])-[C:4]-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[N;H0;D3;+0:12]1-[C:11]-[C:10]-[#7:9]-[C:14]-[C:13]-1
null
[]
null
null
null
null
The title compound was prepared in analogy to example 51, from [1-isopropyl-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-piperazin-1-yl-methanone hydrochloride and 2,2,2-trifluoro-ethanesulfonyl chloride. Off-white solid. MS (m/z): 559.4 (M+H)+. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Secondary amine.Sulfonyl halide
Tertiary amine
C1C[NH]CCN1
C1C[NH]CC[NH]1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1
HCl
null
null
null
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3C(C)C)CC1.O=S(=O)(Cl)CC(F)(F)F>>CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(S(=O)(=O)CC(F)(F)F)CC2)n3C(C)C)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-eb3407d9cc5248b692d8d413b2487919
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3C(C)C)CC1.COC(=O)Cl>>COC(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)ccc3n2C(C)C)CC1
Cl.C(C)(C)N1C(=CC2=CC(=CC=C12)OC1CCN(CC1)C(C)C)C(=O)N1CCNCC1.ClC(=O)OC>>COC(=O)N1CCN(CC1)C(=O)C=1N(C2=CC=C(C=C2C1)OC1CCN(CC1)C(C)C)C(C)C
[NH:5]1[CH2:6][CH2:7][N:8]([C:9](=[O:10])[c:11]2[cH:12][c:13]3[cH:14][c:15]([O:16][CH:17]4[CH2:18][CH2:19][N:20]([CH:21]([CH3:22])[CH3:23])[CH2:24][CH2:25]4)[cH:26][cH:27][c:28]3[n:29]2[CH:30]([CH3:31])[CH3:32])[CH2:33][CH2:34]1.Cl[C:3]([O:2][CH3:1])=[O:4]>>[CH3:1][O:2][C:3](=[O:4])[N:5]1[CH2:6][CH2:7][N:8]([C:9](=[O:1...
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3C(C)C)CC1.COC(=O)Cl
COC(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)ccc3n2C(C)C)CC1
null
null
null
Protection
N-alkylation of secondary amines with alkyl halides
98754a5b02829fe15e66bc7afa63abfcc67bc327dedcd37a6b6b54543d6e3170
d86dc1e6d0e089b3444b62ddfcf4c4822bdac4b60e628553036562518c29adcd
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#8:3]-[C;D1;H3:4].[#7:5]1-[C:6]-[C:7]-[NH;D2;+0:8]-[C:9]-[C:10]-1>>[C;D1;H3:4]-[#8:3]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[N;H0;D3;+0:8]1-[C:7]-[C:6]-[#7:5]-[C:10]-[C:9]-1
null
[]
null
null
null
null
The title compound was prepared in analogy to example 51, from [1-isopropyl-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-piperazin-1-yl-methanone hydrochloride and methyl chloroformate. Light-yellow solid. MS (m/z): 471.3 (M+H)+. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Ether.Secondary amine
Carbamic ester
C1CNCC[NH]1
C1C[NH]CC[NH]1
C1C[NH]CC[NH]1.c1ccc2[nH]ccc2c1.C1CC[NH]CC1
HCl
null
null
null
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3C(C)C)CC1.COC(=O)Cl>>COC(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)ccc3n2C(C)C)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-b553fe7f352442599fb3f72a1466f5d7
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3C(C)C)CC1.CN(C)C(=O)Cl>>CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(C(=O)N(C)C)CC2)n3C(C)C)CC1
Cl.C(C)(C)N1C(=CC2=CC(=CC=C12)OC1CCN(CC1)C(C)C)C(=O)N1CCNCC1.CN(C(=O)Cl)C>>CN(C(=O)N1CCN(CC1)C(=O)C=1N(C2=CC=C(C=C2C1)OC1CCN(CC1)C(C)C)C(C)C)C
[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][cH:11][c:12]3[c:13]([cH:14]2)[cH:15][c:16]([C:17](=[O:18])[N:19]2[CH2:20][CH2:21][NH:22][CH2:28][CH2:29]2)[n:30]3[CH:31]([CH3:32])[CH3:33])[CH2:34][CH2:35]1.Cl[C:23](=[O:24])[N:25]([CH3:26])[CH3:27]>>[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:...
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3C(C)C)CC1.CN(C)C(=O)Cl
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(C(=O)N(C)C)CC2)n3C(C)C)CC1
null
null
null
Acylation
N-alkylation of secondary amines with alkyl halides
dcfba2aa7ca13a6ccdf0aa9e5554d01dee20f5aad8e3132e302a663220e425bb
353c6e1db25433862a8bcf26ca332f6abeb45cb685806584bc65f8cfcb712540
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#7:3](-[C;D1;H3:4])-[C;D1;H3:5].[#7:6]1-[C:7]-[C:8]-[NH;D2;+0:9]-[C:10]-[C:11]-1>>[C;D1;H3:4]-[#7:3](-[C;D1;H3:5])-[C;H0;D3;+0:1](=[O;D1;H0:2])-[N;H0;D3;+0:9]1-[C:8]-[C:7]-[#7:6]-[C:11]-[C:10]-1
null
[]
null
null
null
null
The title compound was prepared in analogy to example 51, from [1-isopropyl-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-piperazin-1-yl-methanone hydrochloride and N,N-dimethylcarbamoyl chloride. Off-white solid. MS (m/z): 484.4 (M+H)+. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Tertiary amide.Secondary amine
Urea
C1C[NH]CCN1
C1C[NH]CC[NH]1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1
HCl
null
null
null
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3C(C)C)CC1.CN(C)C(=O)Cl>>CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(C(=O)N(C)C)CC2)n3C(C)C)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-437296a80f494ff988b45523fbb7fb55
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3C(C)C)CC1.CCN(CC)C(=O)Cl>>CCN(CC)C(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)ccc3n2C(C)C)CC1
Cl.C(C)(C)N1C(=CC2=CC(=CC=C12)OC1CCN(CC1)C(C)C)C(=O)N1CCNCC1.C(C)N(C(=O)Cl)CC>>C(C)N(C(=O)N1CCN(CC1)C(=O)C=1N(C2=CC=C(C=C2C1)OC1CCN(CC1)C(C)C)C(C)C)CC
[NH:8]1[CH2:9][CH2:10][N:11]([C:12](=[O:13])[c:14]2[cH:15][c:16]3[cH:17][c:18]([O:19][CH:20]4[CH2:21][CH2:22][N:23]([CH:24]([CH3:25])[CH3:26])[CH2:27][CH2:28]4)[cH:29][cH:30][c:31]3[n:32]2[CH:33]([CH3:34])[CH3:35])[CH2:36][CH2:37]1.Cl[C:6]([N:3]([CH2:2][CH3:1])[CH2:4][CH3:5])=[O:7]>>[CH3:1][CH2:2][N:3]([CH2:4][CH3:5])[...
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3C(C)C)CC1.CCN(CC)C(=O)Cl
CCN(CC)C(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)ccc3n2C(C)C)CC1
null
null
null
Acylation
N-alkylation of secondary amines with alkyl halides
9f480cf7d56f704fd9b7f19410e93a0b335ca09273ad87dbe310c5462f719bdc
353c6e1db25433862a8bcf26ca332f6abeb45cb685806584bc65f8cfcb712540
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#7:3](-[C:4])-[C:5].[#7:6]1-[C:7]-[C:8]-[NH;D2;+0:9]-[C:10]-[C:11]-1>>[C:4]-[#7:3](-[C:5])-[C;H0;D3;+0:1](=[O;D1;H0:2])-[N;H0;D3;+0:9]1-[C:10]-[C:11]-[#7:6]-[C:7]-[C:8]-1
null
[]
null
null
null
null
The title compound was prepared in analogy to example 51, from [1-isopropyl-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-piperazin-1-yl-methanone hydrochloride and N,N-diethylcarbamoyl chloride. Off-white solid. MS (m/z): 512.5 (M+H)+. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Tertiary amide.Secondary amine
Urea
C1CNCC[NH]1
C1C[NH]CC[NH]1
C1C[NH]CC[NH]1.c1ccc2[nH]ccc2c1.C1CC[NH]CC1
HCl
null
null
null
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3C(C)C)CC1.CCN(CC)C(=O)Cl>>CCN(CC)C(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(C(C)C)CC4)ccc3n2C(C)C)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-07a967d2170243e8be4f2abc93e1bedd
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3C(C)C)CC1.O=S(=O)(Cl)C(F)(F)F>>CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(S(=O)(=O)C(F)(F)F)CC2)n3C(C)C)CC1
Cl.C(C)(C)N1C(=CC2=CC(=CC=C12)OC1CCN(CC1)C(C)C)C(=O)N1CCNCC1.FC(S(=O)(=O)Cl)(F)F>>C(C)(C)N1C(=CC2=CC(=CC=C12)OC1CCN(CC1)C(C)C)C(=O)N1CCN(CC1)S(=O)(=O)C(F)(F)F
[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][cH:11][c:12]3[c:13]([cH:14]2)[cH:15][c:16]([C:17](=[O:18])[N:19]2[CH2:20][CH2:21][NH:22][CH2:30][CH2:31]2)[n:32]3[CH:33]([CH3:34])[CH3:35])[CH2:36][CH2:37]1.Cl[S:23](=[O:24])(=[O:25])[C:26]([F:27])([F:28])[F:29]>>[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2...
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3C(C)C)CC1.O=S(=O)(Cl)C(F)(F)F
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(S(=O)(=O)C(F)(F)F)CC2)n3C(C)C)CC1
null
null
null
Acylation
Sulfonamide synthesis (Schotten-Baumann) secondary amine
c6a995ab9be6571957febbe378833244177e30fd671e64e4e1ffe6f50345cf56
b7aca5a5d690b0846685a854bc946849e1041bfc3965161290b5ffb2821af09e
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
Cl-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[C:4](-[F;D1;H0:5])(-[F;D1;H0:6])-[F;D1;H0:7].[#7:8]1-[C:9]-[C:10]-[NH;D2;+0:11]-[C:12]-[C:13]-1>>[F;D1;H0:5]-[C:4](-[F;D1;H0:6])(-[F;D1;H0:7])-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[N;H0;D3;+0:11]1-[C:10]-[C:9]-[#7:8]-[C:13]-[C:12]-1
null
[]
null
null
null
null
The title compound was prepared in analogy to example 51, from [1-isopropyl-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-piperazin-1-yl-methanone hydrochloride and trifluoromethanesulfonyl chloride. Light-yellow solid. MS (m/z): 545.3 (M+H)+. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Secondary amine.Sulfonyl halide
Tertiary amine
C1C[NH]CCN1
C1C[NH]CC[NH]1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1
HCl
null
null
null
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3C(C)C)CC1.O=S(=O)(Cl)C(F)(F)F>>CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(S(=O)(=O)C(F)(F)F)CC2)n3C(C)C)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-c7201a39bff44238a0369f8fa7b950e0
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3C(C)C)CC1.CN(C)S(=O)(=O)Cl>>CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(S(=O)(=O)N(C)C)CC2)n3C(C)C)CC1
Cl.C(C)(C)N1C(=CC2=CC(=CC=C12)OC1CCN(CC1)C(C)C)C(=O)N1CCNCC1.CN(S(=O)(=O)Cl)C>>CN(S(=O)(=O)N1CCN(CC1)C(=O)C=1N(C2=CC=C(C=C2C1)OC1CCN(CC1)C(C)C)C(C)C)C
[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][CH:7]([O:8][c:9]2[cH:10][cH:11][c:12]3[c:13]([cH:14]2)[cH:15][c:16]([C:17](=[O:18])[N:19]2[CH2:20][CH2:21][NH:22][CH2:29][CH2:30]2)[n:31]3[CH:32]([CH3:33])[CH3:34])[CH2:35][CH2:36]1.Cl[S:23](=[O:24])(=[O:25])[N:26]([CH3:27])[CH3:28]>>[CH3:1][CH:2]([CH3:3])[N:4]1[CH2:5][CH2:6][...
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3C(C)C)CC1.CN(C)S(=O)(=O)Cl
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(S(=O)(=O)N(C)C)CC2)n3C(C)C)CC1
null
null
null
Acylation
Sulfonamide synthesis (Schotten-Baumann) secondary amine
9472b3d472badfbf976c26bebba6611bda86b371cf2a2283d41c5954a87661db
6c2a4c35ccae10843ff928afe56a8d3bc92b152c9bcc4d800e2ad816b6c86d86
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
Cl-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[#7:4](-[C;D1;H3:5])-[C;D1;H3:6].[#7:7]1-[C:8]-[C:9]-[NH;D2;+0:10]-[C:11]-[C:12]-1>>[C;D1;H3:5]-[#7:4](-[C;D1;H3:6])-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[N;H0;D3;+0:10]1-[C:9]-[C:8]-[#7:7]-[C:12]-[C:11]-1
null
[]
null
null
null
null
The title compound was prepared in analogy to example 51, from [1-isopropyl-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-piperazin-1-yl-methanone hydrochloride and dimethylsulfamoyl chloride. Light-yellow foam. MS (m/z): 520.2 (M+H)+. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Secondary amine
Tertiary amine
C1C[NH]CCN1
C1C[NH]CC[NH]1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1
HCl
null
null
null
CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCNCC2)n3C(C)C)CC1.CN(C)S(=O)(=O)Cl>>CC(C)N1CCC(Oc2ccc3c(c2)cc(C(=O)N2CCN(S(=O)(=O)N(C)C)CC2)n3C(C)C)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-63c3ca63d3ed41baa0d4b9fe576da2ca
COC(=O)N1CCNCC1.O=C(O)c1cc2cc(OC3CCN(CC(F)(F)F)CC3)ccc2[nH]1>>COC(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(CC(F)(F)F)CC4)ccc3[nH]2)CC1
FC(CN1CCC(CC1)OC=1C=C2C=C(NC2=CC1)C(=O)O)(F)F.N1(CCNCC1)C(=O)OC>>COC(=O)N1CCN(CC1)C(=O)C=1NC2=CC=C(C=C2C1)OC1CCN(CC1)CC(F)(F)F
[CH3:1][O:2][C:3](=[O:4])[N:5]1[CH2:6][CH2:7][NH:8][CH2:32][CH2:33]1.O[C:9](=[O:10])[c:11]1[cH:12][c:13]2[cH:14][c:15]([O:16][CH:17]3[CH2:18][CH2:19][N:20]([CH2:21][C:22]([F:23])([F:24])[F:25])[CH2:26][CH2:27]3)[cH:28][cH:29][c:30]2[nH:31]1>>[CH3:1][O:2][C:3](=[O:4])[N:5]1[CH2:6][CH2:7][N:8]([C:9](=[O:10])[c:11]2[cH:12...
COC(=O)N1CCNCC1.O=C(O)c1cc2cc(OC3CCN(CC(F)(F)F)CC3)ccc2[nH]1
COC(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(CC(F)(F)F)CC4)ccc3[nH]2)CC1
null
null
null
Acylation
Acylation of Nitrogen Nucleophiles by Carboxylic Acids
be4b86020a065d99e289e528d425e25dd0737bea0f2fd81bb05a4d03f92a7d75
c5e4172490b2731ba9322b68af56376edadc31ce0bb9a3dfdea23a1817a852fd
O=C(c1cc2cc(OC3CCNCC3)ccc2[nH]1)N1CCNCC1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#7;a:5]:[c:6].[#7:7]1-[C:8]-[C:9]-[NH;D2;+0:10]-[C:11]-[C:12]-1>>[O;D1;H0:2]=[C;H0;D3;+0:1](-[N;H0;D3;+0:10]1-[C:9]-[C:8]-[#7:7]-[C:12]-[C:11]-1)-[c:3](:[c:4]):[#7;a:5]:[c:6]
null
[]
null
null
null
null
The title compound was prepared in analogy to example 40b), from 5-[1-(2,2,2-trifluoro-ethyl)-piperidin-4-yloxy]-1H-indole-2-carboxylic acid and methyl piperazine-1-carboxylate. Light yellow solid. MS (m/z): 469.3 (M+H)+. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Secondary amine
Tertiary amide
C1C[NH]CCN1
C1C[NH]CC[NH]1
C1C[NH]CC[NH]1.c1ccc2[nH]ccc2c1.C1CC[NH]CC1
HO-
null
null
null
COC(=O)N1CCNCC1.O=C(O)c1cc2cc(OC3CCN(CC(F)(F)F)CC3)ccc2[nH]1>>COC(=O)N1CCN(C(=O)c2cc3cc(OC4CCN(CC(F)(F)F)CC4)ccc3[nH]2)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-678c86ed5e184ea29bab85536d9aef8e
CCOC(=O)c1cc2cc(O)ccc2[nH]1.OC1CCN(CC(F)(F)F)CC1>>CCOC(=O)c1cc2cc(OC3CCN(CC(F)(F)F)CC3)ccc2[nH]1
OC=1C=C2C=C(NC2=CC1)C(=O)OCC.FC(CN1CCC(CC1)O)(F)F.N(=NC(=O)OC(C)C)C(=O)OC(C)C>>FC(CN1CCC(CC1)OC=1C=C2C=C(NC2=CC1)C(=O)OCC)(F)F
[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]2[cH:9][c:10]([OH:11])[cH:23][cH:24][c:25]2[nH:26]1.O[CH:12]1[CH2:13][CH2:14][N:15]([CH2:16][C:17]([F:18])([F:19])[F:20])[CH2:21][CH2:22]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]2[cH:9][c:10]([O:11][CH:12]3[CH2:13][CH2:14][N:15]([CH2:16][C:17]([F:18])([F:19])[...
CCOC(=O)c1cc2cc(O)ccc2[nH]1.OC1CCN(CC(F)(F)F)CC1
CCOC(=O)c1cc2cc(OC3CCN(CC(F)(F)F)CC3)ccc2[nH]1
null
null
null
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
a9e936b0e9135225700edbab1c7696738b7f1f0756494b6ceeeda63b184d572f
776ba735002e33225fbc578943016110c2c43efefd97bfeea4ec3cc2e2e1532f
c1cc2cc(OC3CCNCC3)ccc2[nH]1
O-[CH;D3;+0:1]1-[C:2]-[C:3]-[#7:4]-[C:5]-[C:6]-1.[OH;D1;+0:7]-[c:8](:[c:9]):[c:10]>>[c:9]:[c:8](-[O;H0;D2;+0:7]-[CH;D3;+0:1]1-[C:2]-[C:3]-[#7:4]-[C:5]-[C:6]-1):[c:10]
null
[]
null
null
null
null
The title compound was prepared in analogy to example 40d), from ethyl 5-hydroxyindole-2-carboxylate and 1-(2,2,2-trifluoro-ethyl)piperidin-4-ol, using diisopropyl azodicarboxylate instead of diethyl azodicarboxylate. Off-white solid. MS (m/z): 371.2 (M+H)+. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Secondary alcohol.Aromatic alcohol
Ether
C1CC[NH]CC1
C1CC[NH]CC1
c1ccc2[nH]ccc2c1.C1CC[NH]CC1
HO-
null
null
null
CCOC(=O)c1cc2cc(O)ccc2[nH]1.OC1CCN(CC(F)(F)F)CC1>>CCOC(=O)c1cc2cc(OC3CCN(CC(F)(F)F)CC3)ccc2[nH]1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-fbec5948a29a4f66ba74d90f261126e9
CN(C)C1(c2ccccc2)CCC(C=O)CC1.Fc1ccc(C[P+](c2ccccc2)(c2ccccc2)c2ccccc2)cc1.[Cl-]>>CN(C)C1(c2ccccc2)CCC(C=Cc2ccc(F)cc2)CC1.Cl
CN(C1(CCC(CC1)C=O)C1=CC=CC=C1)C.[Cl-].FC1=CC=C(C[P+](C2=CC=CC=C2)(C2=CC=CC=C2)C2=CC=CC=C2)C=C1.[K].C(C)(C)(C)[O-]>>Cl.FC1=CC=C(C=C1)C=CC1CCC(CC1)(C1=CC=CC=C1)N(C)C
O=[CH:14][CH:13]1[CH2:12][CH2:11][C:4]([N:2]([CH3:1])[CH3:3])([c:5]2[cH:6][cH:7][cH:8][cH:9][cH:10]2)[CH2:24][CH2:23]1.c1ccc([P+](c2ccccc2)(c2ccccc2)[CH2:15][c:16]2[cH:17][cH:18][c:19]([F:20])[cH:21][cH:22]2)cc1.[Cl-:25]>>[CH3:1][N:2]([CH3:3])[C:4]1([c:5]2[cH:6][cH:7][cH:8][cH:9][cH:10]2)[CH2:11][CH2:12][CH:13]([CH:14]...
CN(C)C1(c2ccccc2)CCC(C=O)CC1.Fc1ccc(C[P+](c2ccccc2)(c2ccccc2)c2ccccc2)cc1.[Cl-]
CN(C)C1(c2ccccc2)CCC(C=Cc2ccc(F)cc2)CC1.Cl
null
null
C1CCOC1
C-C Coupling
OtherReaction
cb5f277ac55a0e763ef643becc05f1522019cc4161daceb249ed2d634b78153b
cedc9d4b791e43eacf8e7ecfa6a98d1dc0438794e96e4f1c4bef436b78f82bd8
C(=CC1CCC(c2ccccc2)CC1)c1ccccc1
O=[CH;D2;+0:1]-[C:2](-[C:3])-[C:4].[Cl-;H0;D0:5].[c:6]:[c:7](-[CH2;D2;+0:8]-[P+](-c1:c:c:c:c:c:1)(-c1:c:c:c:c:c:1)-c1:c:c:c:c:c:1):[c:9]>>[C:3]-[C:2](-[CH;D2;+0:1]=[CH;D2;+0:8]-[c:7](:[c:6]):[c:9])-[C:4].[ClH;D0;+0:5]
null
[]
null
null
30
MINUTE
4-fluorobenzyltriphenyl phosphonium chloride (1.22 g, 3 mmole) was suspended under argon in abs. THF (15 ml) and cooled to −5° C. Potassium-tert-butanolate (337 mg, 3 mmole) dissolved in THF (14 ml) was added dropwise and the mixture post-stirred for 30 min at <0°. 4-dimethylamino-4-phenylcyclohexane carbaldehyde (467 ...
10.6084/m9.figshare.5104873.v1
null
Aldehyde
null
c1ccccc1.c1ccccc1.c1ccccc1
null
c1ccccc1.C1CCCCC1.c1ccccc1
HO-
C1CCOC1
null
0.5
CN(C)C1(c2ccccc2)CCC(C=O)CC1.Fc1ccc(C[P+](c2ccccc2)(c2ccccc2)c2ccccc2)cc1.[Cl-]>C1CCOC1>CN(C)C1(c2ccccc2)CCC(C=Cc2ccc(F)cc2)CC1.Cl
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-b9baa8b938bb4678b620f56fdeca6529
CN(C)C1(c2ccccc2)CCC(C=Cc2ccc(F)cc2)CC1>>CN(C)C1(c2ccccc2)CCC(C=Cc2ccc(F)cc2)CC1.CN(C)C1(c2ccccc2)CCC(C=Cc2ccc(F)cc2)CC1
Cl.FC1=CC=C(C=C1)C=CC1CCC(CC1)(C1=CC=CC=C1)N(C)C>>Cl.FC1=CC=C(C=C1)C=CC1CCC(CC1)(C1=CC=CC=C1)N(C)C.FC1=CC=C(C=C1)C=CC1CCC(CC1)(C1=CC=CC=C1)N(C)C
[CH3:1][N:2]([C:4]1([c:5]2[cH:6][cH:7][cH:8][cH:9][cH:10]2)[CH2:35][CH2:36][CH:37]([CH:38]=[CH:39][c:40]2[cH:22][cH:21][c:19]([F:20])[cH:18][cH:41]2)[CH2:45][CH2:46]1)[CH3:29]>>[CH3:1][N:2]([CH3:3])[C:4]1([c:5]2[cH:6][cH:7][cH:8][cH:9][cH:10]2)[CH2:11][CH2:12][CH:13]([CH:14]=[CH:15][c:16]2[cH:17][cH:18][c:19]([F:20])[c...
CN(C)C1(c2ccccc2)CCC(C=Cc2ccc(F)cc2)CC1
CN(C)C1(c2ccccc2)CCC(C=Cc2ccc(F)cc2)CC1.CN(C)C1(c2ccccc2)CCC(C=Cc2ccc(F)cc2)CC1
null
null
CC(CC)=O
Aromatic Heterocycle Formation
OtherReaction
08a033d2514c88484b05c94ceb1115d3c299505ec196d8cd87e779e6e35794dd
7709ea319235d24cfb5c0056ba368e49dcaf4917f91bb00220f500abe1e9be2a
C(=CC1CCC(c2ccccc2)CC1)c1ccccc1.C(=CC1CCC(c2ccccc2)CC1)c1ccccc1
[C;D1;H3:1]-[N;H0;D3;+0:2](-[CH3;D1;+0:3])-[C;H0;D4;+0:4]1(-[c:5](:[c:6]):[c:7])-[CH2;D2;+0:8]-[C:9]-[CH;D3;+0:10](-[C:11]=[C:12]-[c;H0;D3;+0:13]2:[cH;D2;+0:14]:[c:15]:[c:16](-[F;D1;H0:17]):[cH;D2;+0:18]:[cH;D2;+0:19]:2)-[CH2;D2;+0:20]-[CH2;D2;+0:21]-1>>[#7:22]-[C:23]1(-[c;H0;D3;+0:3](:[c:24]:[c:25]):[c:26]:[c:27])-[C:...
null
[]
null
null
2
HOUR
As described for Example 5, 69 mg of the second most polar diastereoisomer of {4-[2-(4-fluorophenyl)vinyl]-1-phenylcyclohexyl}dimethylamine were also obtained (yellow oil) which were dissolved in 2-butanone (1.5 ml), and subsequently 3.3M ethanolic HCl (194 μl, 0.6 mmole) was added and the mixture stirred for 2 h. Afte...
10.6084/m9.figshare.5104873.v1
null
Tertiary amine
Aromatic halide.Tertiary amine.Tertiary amine
C1CCCCC1.c1ccccc1
C1CCCCC1.c1ccccc1.c1ccccc1.C1CCCCC1.c1ccccc1
c1ccccc1.C1CCCCC1.c1ccccc1.c1ccccc1.C1CCCCC1.c1ccccc1
Other
CC(CC)=O
null
2
CN(C)C1(c2ccccc2)CCC(C=Cc2ccc(F)cc2)CC1>CC(CC)=O>CN(C)C1(c2ccccc2)CCC(C=Cc2ccc(F)cc2)CC1.CN(C)C1(c2ccccc2)CCC(C=Cc2ccc(F)cc2)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-b389fc697dc240099ed29c4eb07b7eba
Cl>>Cl
C(C)OCC.Cl.N1C=C(C2=CC=CC=C12)CC=CC1CCC(CC1)(C1=CC=CC=C1)N(C)C.N1C=C(C2=CC=CC=C12)CC=CC1CCC(CC1)(C1=CC=CC=C1)N(C)C.Cl[Si](C)(C)C>>Cl.N1C=C(C2=CC=CC=C12)CC=CC1CCC(CC1)(C1=CC=CC=C1)N(C)C
[ClH:28]>>[ClH:28]
Cl
Cl
null
null
CC(CC)=O
Miscellaneous
OtherReaction
40ba59785861b8226ce5af6bdcbb9a37f0ff50a8c7ec7d4fc4c524cf906cc65c
56ebed4a8b3cebec83c37a71d68f0c87d1e404ab05a9ce792691e4e18a2379dd
null
null
null
[]
null
null
null
null
As described for Example 8, less polar diastereoisomers of {4-[3-(1H-indol-3-yl)-propenyl]-1-phenylcyclohexyl}dimethylamine were not obtained cleanly. For purification, 750 mg non-polar crude product were suspended in 95 ml water and 1 ml 85% by weight phosphoric acid. The suspension was shaken with diethyl ether (3×20...
10.6084/m9.figshare.5104873.v1
null
null
null
null
null
null
null
CC(CC)=O
null
null
Cl>CC(CC)=O>Cl
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-b451d5cf75864953be053b6145451a1d
BrC(Br)(Br)Br.CC(C)(C)OC(=O)n1cc(C=O)c2ccccc21>>CC(C)(C)OC(=O)n1cc(C=C(Br)Br)c2ccccc21
CCCCCC.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C(C)(C)(C)OC(=O)N1C=C(C2=CC=CC=C12)C=O.BrC(Br)(Br)Br>>C(C)(C)(C)OC(=O)N1C=C(C2=CC=CC=C12)C=C(Br)Br
Br[C:12](Br)([Br:13])[Br:14].O=[CH:11][c:10]1[cH:9][n:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[c:20]2[c:15]1[cH:16][cH:17][cH:18][cH:19]2>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[n:8]1[cH:9][c:10]([CH:11]=[C:12]([Br:13])[Br:14])[c:15]2[cH:16][cH:17][cH:18][cH:19][c:20]12
BrC(Br)(Br)Br.CC(C)(C)OC(=O)n1cc(C=O)c2ccccc21
CC(C)(C)OC(=O)n1cc(C=C(Br)Br)c2ccccc21
null
null
C(Cl)Cl
C-C Coupling
OtherReaction
b27e55226bb2edd452ae488b95081b2b03421ee27be6c3935dbea4c7a5eeb5f6
695d5d1b30a064e72a7d907baf677e910730421b6580cc4e59d378cd6f0be898
c1ccc2[nH]ccc2c1
Br-[C;H0;D4;+0:1](-Br)(-[Br;D1;H0:2])-[Br;D1;H0:3].O=[CH;D2;+0:4]-[c:5]1:[c:6]:[c:7]:[#7;a:8](-[C:9](-[#8:10])=[O;D1;H0:11]):[c:12]:1>>[#8:10]-[C:9](=[O;D1;H0:11])-[#7;a:8]1:[c:7]:[c:6]:[c:5](-[CH;D2;+0:4]=[C;H0;D3;+0:1](-[Br;D1;H0:2])-[Br;D1;H0:3]):[c:12]:1
95.2
[{"value": 95.2, "product": "C(C)(C)(C)OC(=O)N1C=C(C2=CC=CC=C12)C=C(Br)Br", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
1
HOUR
Triphenylphosphane (17.2 g, 65.5 mmole) was added in portions at 0° C., while stirring and within 60 min to a solution of tetrabromocarbon (10.9 g, 32.7 mmole) in DCM (120 ml) and post-stirred for 1 h at 0° C. 3-formyl-indole-1-carboxylic acid-tert-butylester (4 g, 16.4 mmole) dissolved in DCM (30 ml) was subsequently ...
10.6084/m9.figshare.5104873.v1
null
Tertiary halide.Tertiary halide.Tertiary halide.Tertiary halide.Aldehyde
Alkenyl halide.Alkenyl halide
null
null
c1c[nH]c2ccccc12
Br-
C(Cl)Cl
0
1
BrC(Br)(Br)Br.CC(C)(C)OC(=O)n1cc(C=O)c2ccccc21>C(Cl)Cl>CC(C)(C)OC(=O)n1cc(C=C(Br)Br)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-1b6e7812a3de42a88c5b16d0566d6771
CC(=O)Nc1cccc2c1C(=O)OC2=O.CCOc1cc(C(N)CS(C)(=O)=O)ccc1OC>>CCOc1cc(C(CS(C)(=O)=O)N2C(=O)c3cccc(NC(C)=O)c3C2=O)ccc1OC
C(C)OC=1C=C(C=CC1OC)C(CS(=O)(=O)C)N.C(C)(=O)NC1=C2C(C(=O)OC2=O)=CC=C1>>C(C)OC=1C=C(C=CC1OC)C(CS(=O)(=O)C)N1C(C2=CC=CC(=C2C1=O)NC(C)=O)=O
O1[C:14](=[O:15])[c:16]2[cH:17][cH:18][cH:19][c:20]([NH:21][C:22]([CH3:23])=[O:24])[c:25]2[C:26]1=[O:27].[CH3:1][CH2:2][O:3][c:4]1[cH:5][c:6]([CH:7]([CH2:8][S:9]([CH3:10])(=[O:11])=[O:12])[NH2:13])[cH:28][cH:29][c:30]1[O:31][CH3:32]>>[CH3:1][CH2:2][O:3][c:4]1[cH:5][c:6]([CH:7]([CH2:8][S:9]([CH3:10])(=[O:11])=[O:12])[N:...
CC(=O)Nc1cccc2c1C(=O)OC2=O.CCOc1cc(C(N)CS(C)(=O)=O)ccc1OC
CCOc1cc(C(CS(C)(=O)=O)N2C(=O)c3cccc(NC(C)=O)c3C2=O)ccc1OC
null
null
C(C)(=O)O
Acylation
Phthalic anhydride to phthalimide
c3c986d6e09320348d40a4a59ca107882ce771f249842049dc55e55f334c675b
2bbbf7b24648445e31d33a2a26f8618c2067bd23957587cc459f3c45a03ed48a
O=C1c2ccccc2C(=O)N1Cc1ccccc1
[C:1]-[C:2](-[NH2;D1;+0:3])-[c:4].[O;D1;H0:5]=[C;H0;D3;+0:6]1-O-[C;H0;D3;+0:7](=[O;D1;H0:8])-[c:9](:[c:10]):[c:11]-1:[c:12]>>[C:1]-[C:2](-[c:4])-[N;H0;D3;+0:3]1-[C;H0;D3;+0:6](=[O;D1;H0:5])-[c:11](:[c:12]):[c:9](:[c:10])-[C;H0;D3;+0:7]-1=[O;D1;H0:8]
59.3
[{"value": 59.0, "product": "C(C)OC=1C=C(C=CC1OC)C(CS(=O)(=O)C)N1C(C2=CC=CC(=C2C1=O)NC(C)=O)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 59.3, "product": "C(C)OC=1C=C(C=CC1OC)C(CS(=O)(=O)C)N1C(C2=CC=CC(=C2C1=O)NC(C)=O)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A stirred solution of 1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethylamine (1.0 g, 3.7 mmol) and 3-acetamidophthalic anhydride (751 mg, 3.66 mmol) in acetic acid (20 mL) was heated at reflux for 15 h. The solvent was removed in vacuo to yield an oil. Chromatography of the resulting oil yielded the product as a yello...
10.6084/m9.figshare.5104873.v1
null
Anhydride.Ester.Ester.Primary amine
Substituted dicarboximide
c1ccc2c(c1)COC2
c1ccc2c(c1)C[NH]C2
c1ccccc1.c1ccc2c(c1)C[NH]C2
HO-
C(C)(=O)O
null
null
CC(=O)Nc1cccc2c1C(=O)OC2=O.CCOc1cc(C(N)CS(C)(=O)=O)ccc1OC>C(C)(=O)O>CCOc1cc(C(CS(C)(=O)=O)N2C(=O)c3cccc(NC(C)=O)c3C2=O)ccc1OC
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-22faef66200548b3880e574be715cd13
O=C(O)c1cccc([N+](=O)[O-])c1C(=O)O>>Nc1cccc(C(=O)O)c1C(=O)O
[H][H].[H][H].[N+](=O)([O-])C1=C(C(C(=O)O)=CC=C1)C(=O)O.[H][H]>>NC1=C(C(C(=O)O)=CC=C1)C(=O)O
O=[N+:1]([O-])[c:2]1[cH:3][cH:4][cH:5][c:6]([C:7](=[O:8])[OH:9])[c:10]1[C:11](=[O:12])[OH:13]>>[NH2:1][c:2]1[cH:3][cH:4][cH:5][c:6]([C:7](=[O:8])[OH:9])[c:10]1[C:11](=[O:12])[OH:13]
O=C(O)c1cccc([N+](=O)[O-])c1C(=O)O
Nc1cccc(C(=O)O)c1C(=O)O
null
[Pd]
C(C)O
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
c1ccccc1
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]-[C:5](=[O;D1;H0:6])-[O;D1;H1:7]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]-[C:5](=[O;D1;H0:6])-[O;D1;H1:7]
84
[{"value": 84.0, "product": "NC1=C(C(C(=O)O)=CC=C1)C(=O)O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 84.0, "product": "NC1=C(C(C(=O)O)=CC=C1)C(=O)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
13
HOUR
10% Pd/C (2.5 g), 3-nitrophthalic acid (75.0 g, 355 mmol) and ethanol (1.5 L) were charged to a 2.5 L Parr hydrogenator, under a nitrogen atmosphere. Hydrogen was charged to the reaction vessel for up to 55 psi. The mixture was shaken for 13 hours, maintaining hydrogen pressure between 50 and 55 psi. Hydrogen was relea...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1ccccc1
Other
[Pd].C(C)O
null
13
O=C(O)c1cccc([N+](=O)[O-])c1C(=O)O>[Pd].C(C)O>Nc1cccc(C(=O)O)c1C(=O)O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-84a7a6b4fbab40d78942753c14739e12
CC(=O)OC(C)=O.Nc1cccc(C(=O)O)c1C(=O)O>>CC(=O)Nc1cccc2c1C(=O)OC2=O
NC1=C(C(C(=O)O)=CC=C1)C(=O)O.C(C)(=O)OC(C)=O>>C(C)(=O)NC1=C2C(C(=O)OC2=O)=CC=C1
CC(=O)O[C:2]([CH3:1])=[O:3].O[C:14]([c:9]1[cH:8][cH:7][cH:6][c:5]([NH2:4])[c:10]1[C:11](=[O:12])[OH:13])=[O:15]>>[CH3:1][C:2](=[O:3])[NH:4][c:5]1[cH:6][cH:7][cH:8][c:9]2[c:10]1[C:11](=[O:12])[O:13][C:14]2=[O:15]
CC(=O)OC(C)=O.Nc1cccc(C(=O)O)c1C(=O)O
CC(=O)Nc1cccc2c1C(=O)OC2=O
null
null
null
Acylation
OtherReaction
617c13c0fd0733e95edf575c7a45ee818629fb61a4451b32cd2addac5c310e5b
ffc045ed8a9408524e8f5f9dc2e099a8f11ba6601fd402a08d042de24191cf1d
O=C1OC(=O)c2ccccc21
C-C(=O)-O-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3].O-[C;H0;D3;+0:4](=[O;D1;H0:5])-[c:6](:[c:7]):[c:8](-[C:9](=[O;D1;H0:10])-[OH;D1;+0:11]):[c:12](-[NH2;D1;+0:13]):[c:14]>>[C;D1;H3:2]-[C;H0;D3;+0:1](=[O;D1;H0:3])-[NH;D2;+0:13]-[c:12](:[c:14]):[c:8]1:[c:6](:[c:7])-[C;H0;D3;+0:4](=[O;D1;H0:5])-[O;H0;D2;+0:11]-[C:9]-1=[O;D...
61
[{"value": 61.0, "product": "C(C)(=O)NC1=C2C(C(=O)OC2=O)=CC=C1", "details": "PERCENTYIELD", "is_desired": false}]
2.5
CELSIUS
null
null
A 1 L 3-necked round bottom flask was equipped with a mechanical stirrer, thermometer, and condenser and charged with 3-aminophthalic acid (108 g, 596 mmol) and acetic anhydride (550 mL). The reaction mixture was heated to reflux for 3 hours and cooled to ambient temperature and further to 0-5° C. for another 1 hour. T...
10.6084/m9.figshare.5104873.v1
null
Anhydride.Carboxylic acid.Carboxylic acid.Primary amine
Anhydride.Ester.Ester.Secondary amide
null
c1ccc2c(c1)COC2
c1ccc2c(c1)COC2
HO-
null
2.5
null
CC(=O)OC(C)=O.Nc1cccc(C(=O)O)c1C(=O)O>>CC(=O)Nc1cccc2c1C(=O)OC2=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-bc03aed0730246ecae54382a543353ca
CCOc1cc(C(N)CS(C)(=O)=O)ccc1OC>>CCOc1cc([C@H](N)CS(C)(=O)=O)ccc1OC
C(C)OC=1C=C(C=CC1OC)C(CS(=O)(=O)C)N.C(C)(=O)N[C@@H](CC(C)C)C(=O)O>>C(C)(=O)N[C@@H](CC(C)C)C(=O)O.C(C)OC=1C=C(C=CC1OC)[C@@H](CS(=O)(=O)C)N
[CH3:13][CH2:14][O:15][c:16]1[cH:17][c:18]([CH:19]([NH2:20])[CH2:21][S:22]([CH3:23])(=[O:24])=[O:25])[cH:26][cH:27][c:28]1[O:29][CH3:30]>>[CH3:13][CH2:14][O:15][c:16]1[cH:17][c:18]([C@H:19]([NH2:20])[CH2:21][S:22]([CH3:23])(=[O:24])=[O:25])[cH:26][cH:27][c:28]1[O:29][CH3:30]
CCOc1cc(C(N)CS(C)(=O)=O)ccc1OC
CCOc1cc([C@H](N)CS(C)(=O)=O)ccc1OC
null
null
CO
Miscellaneous
OtherReaction
40ba59785861b8226ce5af6bdcbb9a37f0ff50a8c7ec7d4fc4c524cf906cc65c
56ebed4a8b3cebec83c37a71d68f0c87d1e404ab05a9ce792691e4e18a2379dd
c1ccccc1
null
90
[{"value": 90.0, "product": "C(C)(=O)N[C@@H](CC(C)C)C(=O)O.C(C)OC=1C=C(C=CC1OC)[C@@H](CS(=O)(=O)C)N", "details": "PERCENTYIELD", "is_desired": false}, {"value": 37.0, "product": "C(C)(=O)N[C@@H](CC(C)C)C(=O)O.C(C)OC=1C=C(C=CC1OC)[C@@H](CS(=O)(=O)C)N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3
HOUR
A 3 L 3-necked round bottom flask was equipped with a mechanical stirrer, thermometer, and condenser and charged with 2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulphonyl)-eth-2-ylamine (137.0 g, 500 mmol), N-acetyl-L-leucine (52 g, 300 mmol), and methanol (1.0 L). The stirred slurry was heated to reflux for 1 hour. The sti...
10.6084/m9.figshare.5104873.v1
null
null
null
null
null
c1ccccc1
null
CO
null
3
CCOc1cc(C(N)CS(C)(=O)=O)ccc1OC>CO>CCOc1cc([C@H](N)CS(C)(=O)=O)ccc1OC
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a99944e743914f408ab0c52108d16f81
CC(=O)Nc1cccc2c1C(=O)OC2=O.CCOc1cc([C@H](N)CS(C)(=O)=O)ccc1OC>>CCOc1cc(C(CS(C)(=O)=O)N2C(=O)c3cccc(N)c3C2=O)ccc1OC
C(C)(=O)N[C@@H](CC(C)C)C(=O)O.C(C)OC=1C=C(C=CC1OC)[C@@H](CS(=O)(=O)C)N.C(C)(=O)NC1=C2C(C(=O)OC2=O)=CC=C1>>C(C)OC=1C=C(C=CC1OC)C(CS(=O)(=O)C)N1C(C2=CC=CC(=C2C1=O)N)=O
CC(=O)[NH:21][c:20]1[cH:19][cH:18][cH:17][c:16]2[c:22]1[C:23](=[O:24])O[C:14]2=[O:15].[CH3:1][CH2:2][O:3][c:4]1[cH:5][c:6]([C@@H:7]([CH2:8][S:9]([CH3:10])(=[O:11])=[O:12])[NH2:13])[cH:25][cH:26][c:27]1[O:28][CH3:29]>>[CH3:1][CH2:2][O:3][c:4]1[cH:5][c:6]([CH:7]([CH2:8][S:9]([CH3:10])(=[O:11])=[O:12])[N:13]2[C:14](=[O:15...
CC(=O)Nc1cccc2c1C(=O)OC2=O.CCOc1cc([C@H](N)CS(C)(=O)=O)ccc1OC
CCOc1cc(C(CS(C)(=O)=O)N2C(=O)c3cccc(N)c3C2=O)ccc1OC
null
null
C(C)(=O)O
Acylation
OtherReaction
3fcce89fe65d3a59d909d36c6ff10c55d9a99436771d834354e62b57b35184a8
0a142f4ab6dc4e530e33b11a80b96ebde5221dc70ae5f3a91acd13dfc0df8a03
O=C1c2ccccc2C(=O)N1Cc1ccccc1
C-C(=O)-[NH;D2;+0:1]-[c:2](:[c:3]):[c:4]1:[c:5](:[c:6])-[C;H0;D3;+0:7](=[O;D1;H0:8])-O-[C;H0;D3;+0:9]-1=[O;D1;H0:10].[#16:11]-[C:12]-[C@@H;D3;+0:13](-[NH2;D1;+0:14])-[c:15](:[c:16]):[c:17]>>[#16:11]-[C:12]-[CH;D3;+0:13](-[N;H0;D3;+0:14]1-[C;H0;D3;+0:7](=[O;D1;H0:8])-[c:5](:[c:6]):[c:4](:[c:2](-[NH2;D1;+0:1]):[c:3])-[C;...
82.8
[{"value": 75.0, "product": "C(C)OC=1C=C(C=CC1OC)C(CS(=O)(=O)C)N1C(C2=CC=CC(=C2C1=O)N)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 82.8, "product": "C(C)OC=1C=C(C=CC1OC)C(CS(=O)(=O)C)N1C(C2=CC=CC(=C2C1=O)N)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A 500 mL 3-necked round bottom flask was equipped with a mechanical stirrer, thermometer, and condenser. The reaction vessel was charged with (S)-2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulphonyl)-eth-2-yl amine N-acetyl-L-leucine salt (25 g, 56 mmol, 98% ee), 3-acetamidophthalic anhydride (12.1 g 58.8 mmol), and glacial...
10.6084/m9.figshare.5104873.v1
null
Anhydride.Ester.Ester.Secondary amide.Primary amine
Substituted dicarboximide.Primary amine
c1ccc2c(c1)COC2
c1ccc2c(c1)C[NH]C2
c1ccccc1.c1ccc2c(c1)C[NH]C2
HO-
C(C)(=O)O
null
null
CC(=O)Nc1cccc2c1C(=O)OC2=O.CCOc1cc([C@H](N)CS(C)(=O)=O)ccc1OC>C(C)(=O)O>CCOc1cc(C(CS(C)(=O)=O)N2C(=O)c3cccc(N)c3C2=O)ccc1OC
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-25375e3403b849d89b8e5f17ac754ba2
CC(=O)OC(C)=O.Oc1cccc(Cl)c1>>CC(=O)Oc1cccc(Cl)c1
ClC=1C=C(C=CC1)O.C(C)(=O)OC(C)=O.[Na]>>C(C)(=O)OC1=CC(=CC=C1)Cl
CC(=O)O[C:2]([CH3:1])=[O:3].[OH:4][c:5]1[cH:6][cH:7][cH:8][c:9]([Cl:10])[cH:11]1>>[CH3:1][C:2](=[O:3])[O:4][c:5]1[cH:6][cH:7][cH:8][c:9]([Cl:10])[cH:11]1
CC(=O)OC(C)=O.Oc1cccc(Cl)c1
CC(=O)Oc1cccc(Cl)c1
null
S(O)(O)(=O)=O
null
Acylation
Acetic anhydride and alcohol to ester
55f321cc520ab80a97c517ea4db1ffe6ba0ea312e2db70f74b0966421bec0a44
96218bff9f96200922f4dff3481116557fe6986cba41ef7bff8cc8a0b43bd224
c1ccccc1
C-C(=O)-O-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3].[OH;D1;+0:4]-[c:5](:[c:6]):[c:7]>>[C;D1;H3:2]-[C;H0;D3;+0:1](=[O;D1;H0:3])-[O;H0;D2;+0:4]-[c:5](:[c:6]):[c:7]
null
[]
120
CELSIUS
45
MINUTE
3-Chlorophenol (100 g, 0.78 mol) was dissolved in acetic anhydride (75 mL, 0.8 mol). Upon addition of 1 drop of concentrated sulfuric acid, the temperature raised to 120° C. After 45 minutes, the mixture was cooled and poured into a solution of sodium hydrogenocarbonate (8 g in 1 L of water) and extracted with diethyle...
10.6084/m9.figshare.5104873.v1
null
Anhydride.Aromatic alcohol
Ester
null
null
c1ccccc1
HO-
S(O)(O)(=O)=O
120
0.75
CC(=O)OC(C)=O.Oc1cccc(Cl)c1>S(O)(O)(=O)=O>CC(=O)Oc1cccc(Cl)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-4d56cf976bb44648b361f8bf4ea541af
CC(=O)c1ccc(Cl)cc1O.CC(C)=O>>CC1(C)CC(=O)c2ccc(Cl)cc2O1
CC(=O)C1=C(C=C(C=C1)Cl)O.CC(=O)C.N1CCCC1>>ClC1=CC2=C(C(CC(O2)(C)C)=O)C=C1
[CH3:4][C:5](=[O:6])[c:7]1[cH:8][cH:9][c:10]([Cl:11])[cH:12][c:13]1[OH:14].O=[C:2]([CH3:1])[CH3:3]>>[CH3:1][C:2]1([CH3:3])[CH2:4][C:5](=[O:6])[c:7]2[cH:8][cH:9][c:10]([Cl:11])[cH:12][c:13]2[O:14]1
CC(=O)c1ccc(Cl)cc1O.CC(C)=O
CC1(C)CC(=O)c2ccc(Cl)cc2O1
null
null
CO
Heteroatom Alkylation and Arylation
OtherReaction
177c53c6f229e3255e30105214dd5c7935fd1f18d03e441505a34379447ca7ce
2b19ddad93f276f7cba72518a5f5b44fb4fd6e49b358f1173e7b2c08a31b3f60
O=C1CCOc2ccccc21
O=[C;H0;D3;+0:1](-[C;D1;H3:2])-[C;D1;H3:3].[CH3;D1;+0:4]-[C:5](=[O;D1;H0:6])-[c:7]:[c:8](-[OH;D1;+0:9]):[c:10]>>[C;D1;H3:2]-[C;H0;D4;+0:1]1(-[C;D1;H3:3])-[CH2;D2;+0:4]-[C:5](=[O;D1;H0:6])-[c:7]:[c:8](:[c:10])-[O;H0;D2;+0:9]-1
null
[]
null
null
null
null
A solution of 4-chloro-2-hydroxyacetophenone (20 g, 0.1176 mol), acetone (13.3 mL, 0.1811 mol) and pyrrolidine (15 mL, 0.18 mol) in methanol (475 mL) was stirred at 25° C. overnight. The mixture was then concentrated to a red oil. Water was added and the solution was adjusted to pH 1 with concentrated hydrochloric acid...
10.6084/m9.figshare.5104873.v1
null
Ketone.Ketone.Aromatic alcohol
Ketone.Ether
null
c1ccc2c(c1)CCCO2
c1ccc2c(c1)CCCO2
HO-
CO
null
null
CC(=O)c1ccc(Cl)cc1O.CC(C)=O>CO>CC1(C)CC(=O)c2ccc(Cl)cc2O1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-acf9316207ca49a4b73f93a9e869c50a
CC(=O)c1cc(Br)ccc1O.O=C1CCCC1>>O=C1CC2(CCCC2)Oc2ccc(Br)cc21
CC(=O)C1=C(C=CC(=C1)Br)O.C1(CCCC1)=O.N1CCCC1>>BrC=1C=CC2=C(C(CC3(CCCC3)O2)=O)C1
[O:1]=[C:2]([CH3:3])[c:16]1[c:10]([OH:9])[cH:11][cH:12][c:13]([Br:14])[cH:15]1.O=[C:4]1[CH2:5][CH2:6][CH2:7][CH2:8]1>>[O:1]=[C:2]1[CH2:3][C:4]2([CH2:5][CH2:6][CH2:7][CH2:8]2)[O:9][c:10]2[cH:11][cH:12][c:13]([Br:14])[cH:15][c:16]21
CC(=O)c1cc(Br)ccc1O.O=C1CCCC1
O=C1CC2(CCCC2)Oc2ccc(Br)cc21
null
null
CO
Heteroatom Alkylation and Arylation
OtherReaction
54f8457e0ef414d7ecba4bad766f9e864aebfcb56b4f48ae0699e350957831b7
2b19ddad93f276f7cba72518a5f5b44fb4fd6e49b358f1173e7b2c08a31b3f60
O=C1CC2(CCCC2)Oc2ccccc21
O=[C;H0;D3;+0:1]1-[C:2]-[C:3]-[C:4]-[C:5]-1.[CH3;D1;+0:6]-[C:7](=[O;D1;H0:8])-[c:9]:[c:10](-[OH;D1;+0:11]):[c:12]>>[O;D1;H0:8]=[C:7]1-[CH2;D2;+0:6]-[C;H0;D4;+0:1]2(-[C:2]-[C:3]-[C:4]-[C:5]-2)-[O;H0;D2;+0:11]-[c:10](:[c:12]):[c:9]-1
null
[]
null
null
null
null
A solution of 5-bromo-2-hydroxyacetophenone (31.6 g, 0.1477 mol), cyclopentanone (26 mL, 0.2939 mol) and pyrrolidine (24 mL, 0.288 mol) in methanol (600 mL) was stirred at 25° C. overnight. The mixture was then concentrated to a red oil. Water was added and the solution was adjusted to pH 1 with concentrated hydrochlor...
10.6084/m9.figshare.5104873.v1
null
Ketone.Ketone.Aromatic alcohol
Ketone.Ether
C1CCCC1
c1ccc2c(c1)CCC1(CCCC1)O2
c1ccc2c(c1)CCC1(CCCC1)O2
HO-
CO
null
null
CC(=O)c1cc(Br)ccc1O.O=C1CCCC1>CO>O=C1CC2(CCCC2)Oc2ccc(Br)cc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-f0f4ba2f76c247f393accfad4465076f
O=C1CC2(CCCC2)Oc2ccc(Br)cc21>>OC1CC2(CCCC2)Oc2ccc(Br)cc21
[BH4-].[Na+].BrC=1C=CC2=C(C(CC3(CCCC3)O2)=O)C1.Cl>>BrC=1C=CC2=C(C(CC3(CCCC3)O2)O)C1
[O:1]=[C:2]1[CH2:3][C:4]2([CH2:5][CH2:6][CH2:7][CH2:8]2)[O:9][c:10]2[cH:11][cH:12][c:13]([Br:14])[cH:15][c:16]21>>[OH:1][CH:2]1[CH2:3][C:4]2([CH2:5][CH2:6][CH2:7][CH2:8]2)[O:9][c:10]2[cH:11][cH:12][c:13]([Br:14])[cH:15][c:16]21
O=C1CC2(CCCC2)Oc2ccc(Br)cc21
OC1CC2(CCCC2)Oc2ccc(Br)cc21
null
null
CO
Reduction
Reduction of ketone to secondary alcohol
eb0e0d46e51393c1b1c6557345907d37c04068e329616b7f9cbfe08d8cc38897
1bd3cd74b454139c0a0068ac0135836499926b274bff569df163210c6c944a89
c1ccc2c(c1)CCC1(CCCC1)O2
[O;H0;D1;+0:1]=[C;H0;D3;+0:2]1-[C:3]-[C:4]-[#8:5]-[c:6]:[c:7]-1:[c:8]>>[OH;D1;+0:1]-[CH;D3;+0:2]1-[C:3]-[C:4]-[#8:5]-[c:6]:[c:7]-1:[c:8]
null
[]
null
null
30
MINUTE
Sodium borohydride (4.65 g, 0.123 mol) was added to a stirred suspension of 6-bromo-3,4-dihydro-spiro[2H-1-benzopyran-2,1′-cyclopentan]-4-one (31.83 g, 0.1137 mol) in methanol (650 mL) at 0° C. and the mixture was maintained at this temperature for a further 30 minutes. After stirring for an additional 30 minutes at ro...
10.6084/m9.figshare.5104873.v1
null
Ketone
Secondary alcohol
c1ccc2c(c1)CCC1(CCCC1)O2
c1ccc2c(c1)CCC1(CCCC1)O2
c1ccc2c(c1)CCC1(CCCC1)O2
null
CO
null
0.5
O=C1CC2(CCCC2)Oc2ccc(Br)cc21>CO>OC1CC2(CCCC2)Oc2ccc(Br)cc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-e1920ef2f02749dd94be0827329a4137
CN(C)c1cccc(O)c1.N#CCC#N.O=Cc1ccc2c(c1)OCO2>>CN(C)c1ccc2c(c1)OC(N)=C(C#N)C2c1ccc2c(c1)OCO2
N1CCCCC1.CN(C=1C=C(C=CC1)O)C.C1=CC2=C(C=C1C=O)OCO2.C(CC#N)#N>>NC=1OC2=CC(=CC=C2C(C1C#N)C1=CC2=C(C=C1)OCO2)N(C)C
[CH3:1][N:2]([CH3:3])[c:4]1[cH:5][cH:6][cH:7][c:8]([OH:10])[cH:9]1.[C:11](#[N:12])[CH2:13][C:14]#[N:15].O=[CH:16][c:17]1[cH:18][cH:19][c:20]2[c:21]([cH:22]1)[O:23][CH2:24][O:25]2>>[CH3:1][N:2]([CH3:3])[c:4]1[cH:5][cH:6][c:7]2[c:8]([cH:9]1)[O:10][C:11]([NH2:12])=[C:13]([C:14]#[N:15])[CH:16]2[c:17]1[cH:18][cH:19][c:20]2[...
CN(C)c1cccc(O)c1.N#CCC#N.O=Cc1ccc2c(c1)OCO2
CN(C)c1ccc2c(c1)OC(N)=C(C#N)C2c1ccc2c(c1)OCO2
null
null
C(C)O
Acylation
OtherReaction
49e188f97b5969b9740a7436492b0baaa1bf2e17f3288b4209ac7db1391444e0
b60f684fc894decc11bc6e0a45d6754f936c8349174c81d94024a37d26dffaa5
C1=CC(c2ccc3c(c2)OCO3)c2ccccc2O1
O=[CH;D2;+0:1]-[c:2](:[c:3]):[c:4].[N;D1;H0:5]#[C:6]-[CH2;D2;+0:7]-[C;H0;D2;+0:8]#[N;H0;D1;+0:9].[OH;D1;+0:10]-[c:11](:[c:12]):[cH;D2;+0:13]:[c:14]:[c:15]>>[N;D1;H0:5]#[C:6]-[C;H0;D3;+0:7]1=[C;H0;D3;+0:8](-[NH2;D1;+0:9])-[O;H0;D2;+0:10]-[c:11](:[c:12]):[c;H0;D3;+0:13](:[c:14]:[c:15])-[CH;D3;+0:1]-1-[c:2](:[c:3]):[c:4]
79.3
[{"value": 79.0, "product": "NC=1OC2=CC(=CC=C2C(C1C#N)C1=CC2=C(C=C1)OCO2)N(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 79.3, "product": "NC=1OC2=CC(=CC=C2C(C1C#N)C1=CC2=C(C=C1)OCO2)N(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
To a mixture of 3-dimethylaminophenol (489 mg, 3.56 mmol), piperonal (535 mg, 3.56 mmol), and malononitrile (233 mg, 3.53 mmol) in ethanol (20 ml) was added piperidine (0.70 ml, 7.1 mmol). The mixture was stirred at room temperature for 2 h and the resulting solid was collected by filtration, washed with methanol and d...
10.6084/m9.figshare.5104873.v1
null
Aldehyde.Nitrile.Aromatic alcohol
Enamine.Ether
c1ccccc1
C1=COc2ccccc2C1
C1=COc2ccccc2C1.c1ccc2c(c1)OCO2
HO-
C(C)O
null
2
CN(C)c1cccc(O)c1.N#CCC#N.O=Cc1ccc2c(c1)OCO2>C(C)O>CN(C)c1ccc2c(c1)OC(N)=C(C#N)C2c1ccc2c(c1)OCO2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-e966886be5474db9aad6c3016524dfe8
CCC(=O)Cl.CN(C)c1ccc2c(c1)OC(N)=C(C#N)C2c1ccc2c(c1)OCO2>>CCC(=O)NC1=C(C#N)C(c2ccc3c(c2)OCO3)c2ccc(N(C)C)cc2O1
C(CC)(=O)Cl.NC=1OC2=CC(=CC=C2C(C1C#N)C1=CC2=C(C=C1)OCO2)N(C)C.N1=CC=CC=C1>>C(#N)C1=C(OC2=CC(=CC=C2C1C1=CC2=C(C=C1)OCO2)N(C)C)NC(CC)=O
Cl[C:3]([CH2:2][CH3:1])=[O:4].[NH2:5][C:6]1=[C:7]([C:8]#[N:9])[CH:10]([c:11]2[cH:12][cH:13][c:14]3[c:15]([cH:16]2)[O:17][CH2:18][O:19]3)[c:20]2[cH:21][cH:22][c:23]([N:24]([CH3:25])[CH3:26])[cH:27][c:28]2[O:29]1>>[CH3:1][CH2:2][C:3](=[O:4])[NH:5][C:6]1=[C:7]([C:8]#[N:9])[CH:10]([c:11]2[cH:12][cH:13][c:14]3[c:15]([cH:16]...
CCC(=O)Cl.CN(C)c1ccc2c(c1)OC(N)=C(C#N)C2c1ccc2c(c1)OCO2
CCC(=O)NC1=C(C#N)C(c2ccc3c(c2)OCO3)c2ccc(N(C)C)cc2O1
null
null
ClCCl.CCCCCC.CCOC(=O)C
Acylation
Acylation of Nitrogen Nucleophiles by Acyl/Thioacyl/Carbamoyl Halides and Analogs_OS
67a4a916abe1047968b46c9f8f63822c89bf28a1a4f499fb1f5fb567edb4070f
178c607e9acb60b2ba315fc0f5a1f8155b3bc47827f60f3f62cd4667d5360363
C1=CC(c2ccc3c(c2)OCO3)c2ccccc2O1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[C;D1;H3:4].[C:5]-[C:6](-[C:7]#[N;D1;H0:8])=[C:9](-[NH2;D1;+0:10])-[#8:11]-[c:12]>>[C:5]-[C:6](-[C:7]#[N;D1;H0:8])=[C:9](-[NH;D2;+0:10]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[C;D1;H3:4])-[#8:11]-[c:12]
14
[{"value": 14.0, "product": "C(#N)C1=C(OC2=CC(=CC=C2C1C1=CC2=C(C=C1)OCO2)N(C)C)NC(CC)=O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
4
HOUR
To a solution of 2-amino-3-cyano-7-dimethylamino-4-(3,4-methylenedioxyphenyl)-4H-chromene (102 mg, 0.30 mmol) in dichloromethane (5 ml) was added pyridine (0.7 ml) at 0° C., followed by propionyl chloride (0.3 ml). The mixture was then stirred at room temperature for 4 h, diluted with 1:1 hexane/EtOAc (80 ml), washed w...
10.6084/m9.figshare.5104873.v1
null
Enamine.Acyl halide
Enamine.Secondary amide
null
null
c1ccc2c(c1)OCO2.C1=COc2ccccc2C1
HCl
ClCCl.CCCCCC.CCOC(=O)C
null
4
CCC(=O)Cl.CN(C)c1ccc2c(c1)OC(N)=C(C#N)C2c1ccc2c(c1)OCO2>ClCCl.CCCCCC.CCOC(=O)C>CCC(=O)NC1=C(C#N)C(c2ccc3c(c2)OCO3)c2ccc(N(C)C)cc2O1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-b317cfc19b124188b1c578197f6f698d
COc1cc(C2c3ccc(N(C)C)cc3OC(=N)C2C(=O)c2ccccc2)cc2c1OCO2>>COc1cc(C2C(C(=O)c3ccccc3)=C(N)Oc3cc(N(C)C)ccc32)cc2c1OCO2
N=C1OC2=CC(=CC=C2C(C1C(C1=CC=CC=C1)=O)C1=CC(=C2C(=C1)OCO2)OC)N(C)C.C(C)N(CC)CC>>NC=1OC2=CC(=CC=C2C(C1C(C1=CC=CC=C1)=O)C1=CC(=C2C(=C1)OCO2)OC)N(C)C
[CH3:1][O:2][c:3]1[cH:4][c:5]([CH:6]2[CH:7]([C:8](=[O:9])[c:10]3[cH:11][cH:12][cH:13][cH:14][cH:15]3)[C:16](=[NH:17])[O:18][c:19]3[cH:20][c:21]([N:22]([CH3:23])[CH3:24])[cH:25][cH:26][c:27]32)[cH:28][c:29]2[c:30]1[O:31][CH2:32][O:33]2>>[CH3:1][O:2][c:3]1[cH:4][c:5]([CH:6]2[C:7]([C:8](=[O:9])[c:10]3[cH:11][cH:12][cH:13]...
COc1cc(C2c3ccc(N(C)C)cc3OC(=N)C2C(=O)c2ccccc2)cc2c1OCO2
COc1cc(C2C(C(=O)c3ccccc3)=C(N)Oc3cc(N(C)C)ccc32)cc2c1OCO2
null
null
C(C)O
Miscellaneous
OtherReaction
45ba87f560add860ec82d3f9c1a75167fdb400737f2ecedb227dc87b5a69340d
bf7f1a19d2e8b1324c5e79c8242a88993bcd0e4d5a562c8fd4c9cc645aa5a46d
O=C(C1=COc2ccccc2C1c1ccc2c(c1)OCO2)c1ccccc1
[NH;D1;+0:1]=[C;H0;D3;+0:2]1-[#8:3]-[c:4]:[c:5]-[C:6](-[c:7])-[CH;D3;+0:8]-1-[C:9](=[O;D1;H0:10])-[c:11]>>[NH2;D1;+0:1]-[C;H0;D3;+0:2]1=[C;H0;D3;+0:8](-[C:9](=[O;D1;H0:10])-[c:11])-[C:6](-[c:7])-[c:5]:[c:4]-[#8:3]-1
72
[{"value": 72.0, "product": "NC=1OC2=CC(=CC=C2C(C1C(C1=CC=CC=C1)=O)C1=CC(=C2C(=C1)OCO2)OC)N(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 68.6, "product": "NC=1OC2=CC(=CC=C2C(C1C(C1=CC=CC=C1)=O)C1=CC(=C2C(=C1)OCO2)OC)N(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 2-imino-3-benzoyl-7-dimethylamino-4-(3-methoxy-4,5-methylenedioxyphenyl)-chromane (26 mg, 0.059 mmol) and triethylamine (0.1 ml) in ethanol (5 ml) was refluxed for 12 h. It was concentrated, and the residue was purified by column chromatography (silica gel, EtOAc/Hexane=1:5) to give 18 mg (72%) of the tit...
10.6084/m9.figshare.5104873.v1
null
Ketone.Ether
Enamine
c1ccc2c(c1)CCCO2
C1=COc2ccccc2C1
c1ccccc1.C1=COc2ccccc2C1.c1ccc2c(c1)OCO2
null
C(C)O
null
null
COc1cc(C2c3ccc(N(C)C)cc3OC(=N)C2C(=O)c2ccccc2)cc2c1OCO2>C(C)O>COc1cc(C2C(C(=O)c3ccccc3)=C(N)Oc3cc(N(C)C)ccc32)cc2c1OCO2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-d27353f34a1b4168a72fadcaff16e6f7
CC(=O)OC(C)=O.CN(C)c1ccc2c(c1)OC(c1cc3c(c(C#N)c1N)OCO3)=CC2>>CC(=O)Nc1c(C2=CCc3ccc(N(C)C)cc3O2)cc2c(c1C#N)OCO2
NC1=C(C=C2C(=C1C#N)OCO2)C=2OC1=CC(=CC=C1CC2)N(C)C.C(C)(=O)OC(C)=O>>C(C)(=O)NC1=C(C=C2C(=C1C#N)OCO2)C=2OC1=CC(=CC=C1CC2)N(C)C
CC(=O)O[C:2]([CH3:1])=[O:3].[NH2:4][c:5]1[c:6]([C:7]2=[CH:8][CH2:9][c:10]3[cH:11][cH:12][c:13]([N:14]([CH3:15])[CH3:16])[cH:17][c:18]3[O:19]2)[cH:20][c:21]2[c:22]([c:23]1[C:24]#[N:25])[O:26][CH2:27][O:28]2>>[CH3:1][C:2](=[O:3])[NH:4][c:5]1[c:6]([C:7]2=[CH:8][CH2:9][c:10]3[cH:11][cH:12][c:13]([N:14]([CH3:15])[CH3:16])[c...
CC(=O)OC(C)=O.CN(C)c1ccc2c(c1)OC(c1cc3c(c(C#N)c1N)OCO3)=CC2
CC(=O)Nc1c(C2=CCc3ccc(N(C)C)cc3O2)cc2c(c1C#N)OCO2
null
null
N1=CC=CC=C1.CCCCCC.CCOC(=O)C
Acylation
Aminolysis of esters
87d35e51b477fc9a658a6f307eb56d84c8879182772c9dd3a42ec0d584fd2684
627cbc0550c9f51ad0105d9fcf46677e8c93bed87ee95bfe69292a82550c95b7
C1=C(c2ccc3c(c2)OCO3)Oc2ccccc2C1
C-C(=O)-O-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3].[C:4]=[C:5]-[c:6]:[c:7](-[NH2;D1;+0:8]):[c:9]>>[C:4]=[C:5]-[c:6]:[c:7](-[NH;D2;+0:8]-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3]):[c:9]
8.2
[{"value": 8.0, "product": "C(C)(=O)NC1=C(C=C2C(=C1C#N)OCO2)C=2OC1=CC(=CC=C1CC2)N(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 8.2, "product": "C(C)(=O)NC1=C(C=C2C(=C1C#N)OCO2)C=2OC1=CC(=CC=C1CC2)N(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3
DAY
To a solution of 2-amino-3-cyano-7-dimethylamino-4-(methylenedioxy)phenyl-4H-chromene (43 mg, 0.13 mmol) in pyridine (1 ml) was added acetic anhydride (0.25 ml, 2.6 mmol) at room temperature. The mixture was stirred at room temperature for 3 days, then diluted with 1:1 hexane/EtOAc (40 ml), washed with water, 2N HCl, w...
10.6084/m9.figshare.5104873.v1
null
Anhydride.Primary amine
Secondary amide
null
null
C1=COc2ccccc2C1.c1ccc2c(c1)OCO2
HO-
N1=CC=CC=C1.CCCCCC.CCOC(=O)C
null
72
CC(=O)OC(C)=O.CN(C)c1ccc2c(c1)OC(c1cc3c(c(C#N)c1N)OCO3)=CC2>N1=CC=CC=C1.CCCCCC.CCOC(=O)C>CC(=O)Nc1c(C2=CCc3ccc(N(C)C)cc3O2)cc2c(c1C#N)OCO2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-c18e14163bca4fb3aaa3287112574a66
CCOC(=O)Cl.CCOC(C)=O.CN(C)c1ccc2c(c1)OC(c1cc3c(c(C#N)c1N)OCO3)=CC2>>CCOC(=O)N(C(=O)OCC)c1c(C2=CCc3ccc(N(C)C)cc3O2)cc2c(c1C#N)OCO2
CCCCCC.CCOC(=O)C.C(C)OC(=O)Cl.NC1=C(C=C2C(=C1C#N)OCO2)C=2OC1=CC(=CC=C1CC2)N(C)C.N1=CC=CC=C1>>C(#N)C=1C(=C(C=C2C1OCO2)C=2OC1=CC(=CC=C1CC2)N(C)C)N(C(=O)OCC)C(=O)OCC
Cl[C:7](=[O:8])[O:9][CH2:10][CH3:11].C[C:4]([O:3][CH2:2][CH3:1])=[O:5].[NH2:6][c:12]1[c:13]([C:14]2=[CH:15][CH2:16][c:17]3[cH:18][cH:19][c:20]([N:21]([CH3:22])[CH3:23])[cH:24][c:25]3[O:26]2)[cH:27][c:28]2[c:29]([c:30]1[C:31]#[N:32])[O:33][CH2:34][O:35]2>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[N:6]([C:7](=[O:8])[O:9][CH2:10][...
CCOC(=O)Cl.CCOC(C)=O.CN(C)c1ccc2c(c1)OC(c1cc3c(c(C#N)c1N)OCO3)=CC2
CCOC(=O)N(C(=O)OCC)c1c(C2=CCc3ccc(N(C)C)cc3O2)cc2c(c1C#N)OCO2
null
null
C(Cl)Cl
Protection
OtherReaction
45ee5455fcf11e0be4df85e6b2593ba4e1756b905b15ea854e46ef15b9f113b6
35252a2ab228bb8b20a4165ea934452c8cf7700f54d1d2284f6502617da964aa
C1=C(c2ccc3c(c2)OCO3)Oc2ccccc2C1
C-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#8:3]-[C:4].Cl-[C;H0;D3;+0:5](=[O;D1;H0:6])-[#8:7]-[C:8].[C:9]=[C:10]-[c:11]:[c:12](-[NH2;D1;+0:13]):[c:14]>>[C:8]-[#8:7]-[C;H0;D3;+0:5](=[O;D1;H0:6])-[N;H0;D3;+0:13](-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#8:3]-[C:4])-[c:12](:[c:14]):[c:11]-[C:10]=[C:9]
7
[{"value": 7.0, "product": "C(#N)C=1C(=C(C=C2C1OCO2)C=2OC1=CC(=CC=C1CC2)N(C)C)N(C(=O)OCC)C(=O)OCC", "details": "PERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
To a solution of 2-amino-3-cyano-7-dimethylamino-4-(methylenedioxy)phenyl-4H-chromene (53 mg, 0.16 mmol) in methylenechloride (3 ml) was added pyridine (0.06 ml, 0.74 mmol), followed by ethylchloroformate (0.045 ml, 0.47 mmol). The mixture was stirred at room temperature overnight, then diluted with 1:1 hexane/EtOAc (4...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Ester.Ether.Primary amine
Carbamic ester.Carbamic ester
null
null
C1=COc2ccccc2C1.c1ccc2c(c1)OCO2
HCl
C(Cl)Cl
null
8
CCOC(=O)Cl.CCOC(C)=O.CN(C)c1ccc2c(c1)OC(c1cc3c(c(C#N)c1N)OCO3)=CC2>C(Cl)Cl>CCOC(=O)N(C(=O)OCC)c1c(C2=CCc3ccc(N(C)C)cc3O2)cc2c(c1C#N)OCO2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-201c08821a414945bd087660652d455b
COc1cc(C2C(C#N)=C(N)Oc3cc(N)ccc32)cc(Br)c1OC.O=C(Cl)CCl>>COc1cc(C2C(C#N)=C(N)Oc3cc(NC(=O)CCl)ccc32)cc(Br)c1OC
ClCC(=O)Cl.NC=1OC2=CC(=CC=C2C(C1C#N)C1=CC(=C(C(=C1)OC)OC)Br)N.C(C)(C)N(C(C)C)CC>>NC=1OC2=CC(=CC=C2C(C1C#N)C1=CC(=C(C(=C1)OC)OC)Br)NC(CCl)=O
[CH3:1][O:2][c:3]1[cH:4][c:5]([CH:6]2[C:7]([C:8]#[N:9])=[C:10]([NH2:11])[O:12][c:13]3[cH:14][c:15]([NH2:16])[cH:21][cH:22][c:23]32)[cH:24][c:25]([Br:26])[c:27]1[O:28][CH3:29].Cl[C:17](=[O:18])[CH2:19][Cl:20]>>[CH3:1][O:2][c:3]1[cH:4][c:5]([CH:6]2[C:7]([C:8]#[N:9])=[C:10]([NH2:11])[O:12][c:13]3[cH:14][c:15]([NH:16][C:17...
COc1cc(C2C(C#N)=C(N)Oc3cc(N)ccc32)cc(Br)c1OC.O=C(Cl)CCl
COc1cc(C2C(C#N)=C(N)Oc3cc(NC(=O)CCl)ccc32)cc(Br)c1OC
null
null
ClCCl.O.C(C)(=O)OCC
Acylation
Acylation of Nitrogen Nucleophiles by Acyl/Thioacyl/Carbamoyl Halides and Analogs_OS
38143a4d536201990008fd6f2c68e6571a341d1c367481869fbbbe36cb038937
0e6ae078978e324f714e184b4f72826d4e3bf2d9ab22d6e9f73740af687be16f
C1=CC(c2ccccc2)c2ccccc2O1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[Cl;D1;H0:4].[NH2;D1;+0:5]-[c:6](:[c:7]):[c:8]>>[Cl;D1;H0:4]-[C:3]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:5]-[c:6](:[c:7]):[c:8]
24
[{"value": 24.0, "product": "NC=1OC2=CC(=CC=C2C(C1C#N)C1=CC(=C(C(=C1)OC)OC)Br)NC(CCl)=O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
3
HOUR
To a solution of 2,7-diamino-3-cyano-4-(3-bromo-4,5-dimethoxy phenyl)-4H-chromene (50 mg, 0.124 mmol) in dichloromethane (2 ml) was added N,N-diisopropylethylamine (0.043 ml, 0.247 mmol). The flask was cooled in iced water and a solution of chloroacetyl chloride (14 mg, 0.124 mmol) in dichloromethane (1 ml) was added d...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Primary amine
Secondary amide
null
null
c1ccccc1.C1=COc2ccccc2C1
HCl
ClCCl.O.C(C)(=O)OCC
null
3
COc1cc(C2C(C#N)=C(N)Oc3cc(N)ccc32)cc(Br)c1OC.O=C(Cl)CCl>ClCCl.O.C(C)(=O)OCC>COc1cc(C2C(C#N)=C(N)Oc3cc(NC(=O)CCl)ccc32)cc(Br)c1OC
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-2ff9eab2003048e3b6321905acbed681
COc1cc(C2C(C#N)=C(N)Oc3cc(N(C)C)ccc32)cc(Br)c1OC.O=C(Cl)CCl>>COc1cc(C2C(C#N)=C(NC(=O)CCl)Oc3cc(N(C)C)ccc32)cc(Br)c1OC
NC=1OC2=CC(=CC=C2C(C1C#N)C1=CC(=C(C(=C1)OC)OC)Br)N(C)C.ClCC(=O)Cl>>ClCC(=O)NC=1OC2=CC(=CC=C2C(C1C#N)C1=CC(=C(C(=C1)OC)OC)Br)N(C)C
[CH3:1][O:2][c:3]1[cH:4][c:5]([CH:6]2[C:7]([C:8]#[N:9])=[C:10]([NH2:11])[O:16][c:17]3[cH:18][c:19]([N:20]([CH3:21])[CH3:22])[cH:23][cH:24][c:25]32)[cH:26][c:27]([Br:28])[c:29]1[O:30][CH3:31].Cl[C:12](=[O:13])[CH2:14][Cl:15]>>[CH3:1][O:2][c:3]1[cH:4][c:5]([CH:6]2[C:7]([C:8]#[N:9])=[C:10]([NH:11][C:12](=[O:13])[CH2:14][C...
COc1cc(C2C(C#N)=C(N)Oc3cc(N(C)C)ccc32)cc(Br)c1OC.O=C(Cl)CCl
COc1cc(C2C(C#N)=C(NC(=O)CCl)Oc3cc(N(C)C)ccc32)cc(Br)c1OC
null
null
null
Acylation
Acylation of Nitrogen Nucleophiles by Acyl/Thioacyl/Carbamoyl Halides and Analogs_OS
67a4a916abe1047968b46c9f8f63822c89bf28a1a4f499fb1f5fb567edb4070f
178c607e9acb60b2ba315fc0f5a1f8155b3bc47827f60f3f62cd4667d5360363
C1=CC(c2ccccc2)c2ccccc2O1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[Cl;D1;H0:4].[C:5]-[C:6](-[C:7]#[N;D1;H0:8])=[C:9](-[NH2;D1;+0:10])-[#8:11]-[c:12]>>[C:5]-[C:6](-[C:7]#[N;D1;H0:8])=[C:9](-[NH;D2;+0:10]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[Cl;D1;H0:4])-[#8:11]-[c:12]
null
[]
null
null
null
null
The title compound was prepared from 2-amino-3-cyano-7-dimethylamino-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene and chloroacetyl chloride as a yellow solid by a procedure similar to that described for Example 80. 1H NMR (CDCl3): 8.26 (s, 1H), 6.97-6.80 (m, 3H), 6.50-6.46 (m, 1H), 6.33 (d, J=2.4, 1H), 4.73 (s, 3H), 4.2...
10.6084/m9.figshare.5104873.v1
null
Enamine.Acyl halide
Enamine.Secondary amide
null
null
c1ccccc1.C1=COc2ccccc2C1
HCl
null
null
null
COc1cc(C2C(C#N)=C(N)Oc3cc(N(C)C)ccc32)cc(Br)c1OC.O=C(Cl)CCl>>COc1cc(C2C(C#N)=C(NC(=O)CCl)Oc3cc(N(C)C)ccc32)cc(Br)c1OC
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-562ff9997ada41358d60dd652982a399
C=CC(=O)Cl.COc1cc(C2C(C#N)=C(N)Oc3cc(N(C)C)ccc32)cc(Br)c1OC>>C=CC(=O)NC1=C(C#N)C(c2cc(Br)c(OC)c(OC)c2)c2ccc(N(C)C)cc2O1
NC=1OC2=CC(=CC=C2C(C1C#N)C1=CC(=C(C(=C1)OC)OC)Br)N(C)C.C(C=C)(=O)Cl>>C(C=C)(=O)NC=1OC2=CC(=CC=C2C(C1C#N)C1=CC(=C(C(=C1)OC)OC)Br)N(C)C
Cl[C:3]([CH:2]=[CH2:1])=[O:4].[NH2:5][C:6]1=[C:7]([C:8]#[N:9])[CH:10]([c:11]2[cH:12][c:13]([Br:14])[c:15]([O:16][CH3:17])[c:18]([O:19][CH3:20])[cH:21]2)[c:22]2[cH:23][cH:24][c:25]([N:26]([CH3:27])[CH3:28])[cH:29][c:30]2[O:31]1>>[CH2:1]=[CH:2][C:3](=[O:4])[NH:5][C:6]1=[C:7]([C:8]#[N:9])[CH:10]([c:11]2[cH:12][c:13]([Br:1...
C=CC(=O)Cl.COc1cc(C2C(C#N)=C(N)Oc3cc(N(C)C)ccc32)cc(Br)c1OC
C=CC(=O)NC1=C(C#N)C(c2cc(Br)c(OC)c(OC)c2)c2ccc(N(C)C)cc2O1
null
null
null
Acylation
Acylation of Nitrogen Nucleophiles by Acyl/Thioacyl/Carbamoyl Halides and Analogs_OS
67a4a916abe1047968b46c9f8f63822c89bf28a1a4f499fb1f5fb567edb4070f
178c607e9acb60b2ba315fc0f5a1f8155b3bc47827f60f3f62cd4667d5360363
C1=CC(c2ccccc2)c2ccccc2O1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]=[C;D1;H2:4].[C:5]-[C:6](-[C:7]#[N;D1;H0:8])=[C:9](-[NH2;D1;+0:10])-[#8:11]-[c:12]>>[C:5]-[C:6](-[C:7]#[N;D1;H0:8])=[C:9](-[NH;D2;+0:10]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]=[C;D1;H2:4])-[#8:11]-[c:12]
null
[]
null
null
null
null
The title compound was prepared from 2-amino-3-cyano-7-dimethylamino-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene and acryloyl chloride as a yellow solid by a procedure similar to that described for Example 80. 1H NMR (CDCl3): 6.96-6.23 (m, 7H), 5.92 (d, J=10.2, 1H), 4.73 (s, 1H), 3.87 (s, 3H), 3.85 (s, 3H), 2.96 (s, 6H...
10.6084/m9.figshare.5104873.v1
null
Enamine.Acyl halide
Enamine.Secondary amide
null
null
c1ccccc1.C1=COc2ccccc2C1
HCl
null
null
null
C=CC(=O)Cl.COc1cc(C2C(C#N)=C(N)Oc3cc(N(C)C)ccc32)cc(Br)c1OC>>C=CC(=O)NC1=C(C#N)C(c2cc(Br)c(OC)c(OC)c2)c2ccc(N(C)C)cc2O1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-58f8c0ca330b4f2b9b5a9aebfe77c59f
COc1cc(C2C(C#N)=C(N)Oc3cc(N(C)C)ccc32)cc(Br)c1OC.O=C(Cl)CCC(=O)Cl>>COc1cc(C2C(C#N)=C(N3C(=O)CCC3=O)Oc3cc(N(C)C)ccc32)cc(Br)c1OC
NC=1OC2=CC(=CC=C2C(C1C#N)C1=CC(=C(C(=C1)OC)OC)Br)N(C)C.C(CCC(=O)Cl)(=O)Cl>>C(#N)C1=C(OC2=CC(=CC=C2C1C1=CC(=C(C(=C1)OC)OC)Br)N(C)C)N1C(CCC1=O)=O
[CH3:1][O:2][c:3]1[cH:4][c:5]([CH:6]2[C:7]([C:8]#[N:9])=[C:10]([NH2:11])[O:18][c:19]3[cH:20][c:21]([N:22]([CH3:23])[CH3:24])[cH:25][cH:26][c:27]32)[cH:28][c:29]([Br:30])[c:31]1[O:32][CH3:33].Cl[C:12](=[O:13])[CH2:14][CH2:15][C:16](Cl)=[O:17]>>[CH3:1][O:2][c:3]1[cH:4][c:5]([CH:6]2[C:7]([C:8]#[N:9])=[C:10]([N:11]3[C:12](...
COc1cc(C2C(C#N)=C(N)Oc3cc(N(C)C)ccc32)cc(Br)c1OC.O=C(Cl)CCC(=O)Cl
COc1cc(C2C(C#N)=C(N3C(=O)CCC3=O)Oc3cc(N(C)C)ccc32)cc(Br)c1OC
null
null
null
Acylation
OtherReaction
7d15395d78c281a9616558a40d468741555ea5d9291ddf4bae6f7b5a6f8a00d6
29157ec0c8fd9dbe195d2dcc3b2fc6ab025cc069cbb3df87e2beb54a124ad28f
O=C1CCC(=O)N1C1=CC(c2ccccc2)c2ccccc2O1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[C:4]-[C;H0;D3;+0:5](-Cl)=[O;D1;H0:6].[C:7]-[C:8](-[C:9]#[N;D1;H0:10])=[C:11](-[NH2;D1;+0:12])-[#8:13]-[c:14]>>[C:7]-[C:8](-[C:9]#[N;D1;H0:10])=[C:11](-[N;H0;D3;+0:12]1-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[C:4]-[C;H0;D3;+0:5]-1=[O;D1;H0:6])-[#8:13]-[c:14]
null
[]
null
null
null
null
The title compound was prepared from 2-amino-3-cyano-7-dimethylamino-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene and succinyl chloride as a yellow solid by a procedure similar to that described for Example 80. 1H NMR (CDCl3): 7.12 (d, J=1.8, 1H), 6.89-6.85 (m, 2H), 6.47 (m, 1H), 6.26 (d, J=2.7, 1H), 4.79 (s, 1H), 3.87 ...
10.6084/m9.figshare.5104873.v1
null
Enamine.Acyl halide.Acyl halide
Enamine.Substituted dicarboximide
null
C1CC[NH]C1
c1ccccc1.C1CC[NH]C1.C1=COc2ccccc2C1
HCl
null
null
null
COc1cc(C2C(C#N)=C(N)Oc3cc(N(C)C)ccc32)cc(Br)c1OC.O=C(Cl)CCC(=O)Cl>>COc1cc(C2C(C#N)=C(N3C(=O)CCC3=O)Oc3cc(N(C)C)ccc32)cc(Br)c1OC
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-d9a3a53e3d734a35b41bdca07ea9ab63
COc1cc(C=O)cc(Br)c1OC.N#CCC#N.Oc1cccc2ncccc12>>COc1cc(C2C(C#N)=C(N)Oc3c2ccc2ncccc32)cc(Br)c1OC
BrC=1C(=C(C=C(C=O)C1)OC)OC.C(CC#N)#N.N1CCCCC1.OC1=C2C=CC=NC2=CC=C1.N1CCCCC1>>NC1=C(C(C2=C(O1)C=1C=CC=NC1C=C2)C2=CC(=C(C(=C2)OC)OC)Br)C#N
O=[CH:6][c:5]1[cH:4][c:3]([O:2][CH3:1])[c:26]([O:27][CH3:28])[c:24]([Br:25])[cH:23]1.[CH2:7]([C:8]#[N:9])[C:10]#[N:11].[OH:12][c:13]1[cH:14][cH:15][cH:16][c:17]2[n:18][cH:19][cH:20][cH:21][c:22]12>>[CH3:1][O:2][c:3]1[cH:4][c:5]([CH:6]2[C:7]([C:8]#[N:9])=[C:10]([NH2:11])[O:12][c:13]3[c:14]2[cH:15][cH:16][c:17]2[n:18][cH...
COc1cc(C=O)cc(Br)c1OC.N#CCC#N.Oc1cccc2ncccc12
COc1cc(C2C(C#N)=C(N)Oc3c2ccc2ncccc32)cc(Br)c1OC
null
null
C(C)O
Acylation
OtherReaction
8feabb3dfb0e416e3ac80df630c2adede4d565a7eb79cb5cd201fcb8127fa80c
b60f684fc894decc11bc6e0a45d6754f936c8349174c81d94024a37d26dffaa5
C1=CC(c2ccccc2)c2ccc3ncccc3c2O1
O=[CH;D2;+0:1]-[c:2](:[c:3]):[c:4].[#7;a:5]:[c:6]1:[c:7]:[c:8]:[cH;D2;+0:9]:[c:10](-[OH;D1;+0:11]):[c:12]:1.[N;D1;H0:13]#[C:14]-[CH2;D2;+0:15]-[C;H0;D2;+0:16]#[N;H0;D1;+0:17]>>[#7;a:5]:[c:6]1:[c:7]:[c:8]:[c;H0;D3;+0:9]2:[c:10](:[c:12]:1)-[O;H0;D2;+0:11]-[C;H0;D3;+0:16](-[NH2;D1;+0:17])=[C;H0;D3;+0:15](-[C:14]#[N;D1;H0:...
11.4
[{"value": 11.0, "product": "NC1=C(C(C2=C(O1)C=1C=CC=NC1C=C2)C2=CC(=C(C(=C2)OC)OC)Br)C#N", "details": "PERCENTYIELD", "is_desired": false}, {"value": 11.4, "product": "NC1=C(C(C2=C(O1)C=1C=CC=NC1C=C2)C2=CC(=C(C(=C2)OC)OC)Br)C#N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
15
MINUTE
To a mixture of 5-bromoveratraldehyde (245 mg, 1 mmol) and malononitrile (66 mg, 1 mmol) in ethanol (2 ml) was added piperidine (0.1 ml, 1 mmol). The mixture was stirred at room temperature for 15 min, then refluxed for 1 h, and cooled to room temperature. To the mixture was added piperidine (0.1 ml, 1 mmol) and 5-hydr...
10.6084/m9.figshare.5104873.v1
null
Aldehyde.Nitrile.Aromatic alcohol
Enamine.Ether
c1ccc2ncccc2c1
C1=COc2c(ccc3ncccc23)C1
c1ccccc1.C1=COc2c(ccc3ncccc23)C1
HO-
C(C)O
null
0.25
COc1cc(C=O)cc(Br)c1OC.N#CCC#N.Oc1cccc2ncccc12>C(C)O>COc1cc(C2C(C#N)=C(N)Oc3c2ccc2ncccc32)cc(Br)c1OC
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-b282559e2fdd442e84eef5ad9ae52f05
CCOc1cccc(O)c1.COc1cc(C=O)cc(Br)c1OC.N#CCC#N>>CCOc1ccc2c(c1)OC(N)=C(C#N)C2c1cc(Br)c(OC)c(OC)c1
C(C)OC=1C=C(C=CC1)O.BrC=1C(=C(C=C(C=O)C1)OC)OC.C(CC#N)#N.N1CCCCC1>>NC=1OC2=CC(=CC=C2C(C1C#N)C1=CC(=C(C(=C1)OC)OC)Br)OCC
[CH3:1][CH2:2][O:3][c:4]1[cH:5][cH:6][cH:7][c:8]([OH:10])[cH:9]1.O=[CH:16][c:17]1[cH:18][c:19]([Br:20])[c:21]([O:22][CH3:23])[c:24]([O:25][CH3:26])[cH:27]1.[C:11](#[N:12])[CH2:13][C:14]#[N:15]>>[CH3:1][CH2:2][O:3][c:4]1[cH:5][cH:6][c:7]2[c:8]([cH:9]1)[O:10][C:11]([NH2:12])=[C:13]([C:14]#[N:15])[CH:16]2[c:17]1[cH:18][c:...
CCOc1cccc(O)c1.COc1cc(C=O)cc(Br)c1OC.N#CCC#N
CCOc1ccc2c(c1)OC(N)=C(C#N)C2c1cc(Br)c(OC)c(OC)c1
null
null
C(C)O
Acylation
OtherReaction
49e188f97b5969b9740a7436492b0baaa1bf2e17f3288b4209ac7db1391444e0
b60f684fc894decc11bc6e0a45d6754f936c8349174c81d94024a37d26dffaa5
C1=CC(c2ccccc2)c2ccccc2O1
O=[CH;D2;+0:1]-[c:2](:[c:3]):[c:4].[N;D1;H0:5]#[C:6]-[CH2;D2;+0:7]-[C;H0;D2;+0:8]#[N;H0;D1;+0:9].[OH;D1;+0:10]-[c:11](:[c:12]):[cH;D2;+0:13]:[c:14]:[c:15]>>[N;D1;H0:5]#[C:6]-[C;H0;D3;+0:7]1=[C;H0;D3;+0:8](-[NH2;D1;+0:9])-[O;H0;D2;+0:10]-[c:11](:[c:12]):[c;H0;D3;+0:13](:[c:14]:[c:15])-[CH;D3;+0:1]-1-[c:2](:[c:3]):[c:4]
null
[]
null
null
15
MINUTE
To a mixture of 5-bromoveratraldehyde (245 mg, 1 mmol) and malononitrile (66 mg, 1 mmol) in ethanol (2 ml) was added piperidine (0.1 ml, 1 mmol). The mixture was stirred at room temperature for 15 min, then 3-ethoxyphenol (138 mg, 1 mmol) was added and it was stirred overnight. The solvent was evaporated and the residu...
10.6084/m9.figshare.5104873.v1
null
Aldehyde.Nitrile.Aromatic alcohol
Enamine.Ether
c1ccccc1
C1=COc2ccccc2C1
C1=COc2ccccc2C1.c1ccccc1
HO-
C(C)O
null
0.25
CCOc1cccc(O)c1.COc1cc(C=O)cc(Br)c1OC.N#CCC#N>C(C)O>CCOc1ccc2c(c1)OC(N)=C(C#N)C2c1cc(Br)c(OC)c(OC)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a074e92f266541c7b358a10c1af19b40
COc1cc(C=O)cc(Br)c1OC.N#CCC#N>>COc1cc(C=C(C#N)C#N)cc(Br)c1OC
BrC=1C(=C(C=C(C=O)C1)OC)OC.C(CC#N)#N.N1CCCCC1>>COC=1C=C(C=C(C#N)C#N)C=C(C1OC)Br
O=[CH:6][c:5]1[cH:4][c:3]([O:2][CH3:1])[c:15]([O:16][CH3:17])[c:13]([Br:14])[cH:12]1.[CH2:7]([C:8]#[N:9])[C:10]#[N:11]>>[CH3:1][O:2][c:3]1[cH:4][c:5]([CH:6]=[C:7]([C:8]#[N:9])[C:10]#[N:11])[cH:12][c:13]([Br:14])[c:15]1[O:16][CH3:17]
COc1cc(C=O)cc(Br)c1OC.N#CCC#N
COc1cc(C=C(C#N)C#N)cc(Br)c1OC
null
null
C(C)O
C-C Coupling
Knoevenagel Condensation
43d4e2f03e758941ee99f59641d5d56e6475fe935434d251d75d5cdebbe19869
cedc9d4b791e43eacf8e7ecfa6a98d1dc0438794e96e4f1c4bef436b78f82bd8
c1ccccc1
O=[CH;D2;+0:1]-[c:2](:[c:3]):[c:4].[N;D1;H0:5]#[C:6]-[CH2;D2;+0:7]-[C:8]#[N;D1;H0:9]>>[N;D1;H0:5]#[C:6]-[C;H0;D3;+0:7](-[C:8]#[N;D1;H0:9])=[CH;D2;+0:1]-[c:2](:[c:3]):[c:4]
null
[]
null
null
15
MINUTE
To a mixture of 5-bromoveratraldehyde (245 mg, 1 mmol) and malononitrile (66 mg, 1 mmol) in ethanol was added piperidine (0.1 ml, 1 mmol). The mixture was stirred at room temperature for 15 min to give the product 3,4-dimethoxy-5-bromobenzylidenemalononitrile as a yellow precipitate. Conditions: See reaction.notes.proc...
10.6084/m9.figshare.5104873.v1
null
Aldehyde
null
null
null
c1ccccc1
HO-
C(C)O
null
0.25
COc1cc(C=O)cc(Br)c1OC.N#CCC#N>C(C)O>COc1cc(C=C(C#N)C#N)cc(Br)c1OC
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-38a4490365184c17bf9ebd83390c64c8
COc1cc(C=C(C#N)C#N)cc(Br)c1OC.Oc1cccc2c1CCCC2>>COc1cc(C2C(C#N)=C(N)Oc3c2ccc2c3CCCC2)cc(Br)c1OC
COC=1C=C(C=C(C#N)C#N)C=C(C1OC)Br.C1(=CC=CC=2CCCCC12)O.N1CCCCC1>>NC1=C(C(C2=C(O1)C=1CCCCC1C=C2)C2=CC(=C(C(=C2)OC)OC)Br)C#N
[CH3:1][O:2][c:3]1[cH:4][c:5]([CH:6]=[C:7]([C:8]#[N:9])[C:10]#[N:11])[cH:23][c:24]([Br:25])[c:26]1[O:27][CH3:28].[OH:12][c:13]1[cH:14][cH:15][cH:16][c:17]2[c:18]1[CH2:19][CH2:20][CH2:21][CH2:22]2>>[CH3:1][O:2][c:3]1[cH:4][c:5]([CH:6]2[C:7]([C:8]#[N:9])=[C:10]([NH2:11])[O:12][c:13]3[c:14]2[cH:15][cH:16][c:17]2[c:18]3[CH...
COc1cc(C=C(C#N)C#N)cc(Br)c1OC.Oc1cccc2c1CCCC2
COc1cc(C2C(C#N)=C(N)Oc3c2ccc2c3CCCC2)cc(Br)c1OC
null
null
C(C)O
Acylation
OtherReaction
a94361ed2aa33ffb583f60fe41e504a358046c07f64e58249dd1f70a86e8505d
ddf492156ebbbd95b0675ccdaeb616c1c2acd58502f5ae6be273b2a40457d4ef
C1=CC(c2ccccc2)c2ccc3c(c2O1)CCCC3
[N;D1;H0:1]#[C:2]-[C;H0;D3;+0:3](-[C;H0;D2;+0:4]#[N;H0;D1;+0:5])=[CH;D2;+0:6]-[c:7](:[c:8]):[c:9].[OH;D1;+0:10]-[c:11](:[c:12]):[cH;D2;+0:13]:[c:14]:[c:15]>>[N;D1;H0:1]#[C:2]-[C;H0;D3;+0:3]1=[C;H0;D3;+0:4](-[NH2;D1;+0:5])-[O;H0;D2;+0:10]-[c:11](:[c:12]):[c;H0;D3;+0:13](:[c:14]:[c:15])-[CH;D3;+0:6]-1-[c:7](:[c:8]):[c:9]
1.4
[{"value": 1.4, "product": "NC1=C(C(C2=C(O1)C=1CCCCC1C=C2)C2=CC(=C(C(=C2)OC)OC)Br)C#N", "details": "PERCENTYIELD", "is_desired": false}, {"value": 1.4, "product": "NC1=C(C(C2=C(O1)C=1CCCCC1C=C2)C2=CC(=C(C(=C2)OC)OC)Br)C#N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
To a stirred suspension of 3,4-dimethoxy-5-bromobenzylidenemalononitrile (293 mg, 1 mmol) and 5,6,7,8-Tetrahydro-1-naphthol (148 mg, 1 mmol) in ethanol (4 ml) was added piperidine (0.1 ml, 1 mmol), and the mixture was refluxed for 2 h. The solvent was evaporated and the residue was purified by column chromatography (Et...
10.6084/m9.figshare.5104873.v1
null
Nitrile.Aromatic alcohol
Enamine.Ether
c1ccc2c(c1)CCCC2
C1=COc2c(ccc3c2CCCC3)C1
c1ccccc1.C1=COc2c(ccc3c2CCCC3)C1
null
C(C)O
null
null
COc1cc(C=C(C#N)C#N)cc(Br)c1OC.Oc1cccc2c1CCCC2>C(C)O>COc1cc(C2C(C#N)=C(N)Oc3c2ccc2c3CCCC2)cc(Br)c1OC
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a7e5b2eb35eb40ad98877d39ad88aeca
COc1cc(C=C(C#N)C#N)cc(OC)c1OC.Oc1cccc2ncccc12>>COc1cc(C2C(C#N)=C(N)Oc3c2ccc2ncccc32)cc(OC)c1OC
COC=1C=C(C=C(C#N)C#N)C=C(C1OC)OC.OC1=C2C=CC=NC2=CC=C1>>NC1=C(C(C2=C(O1)C=1C=CC=NC1C=C2)C2=CC(=C(C(=C2)OC)OC)OC)C#N
[CH3:1][O:2][c:3]1[cH:4][c:5]([CH:6]=[C:7]([C:8]#[N:9])[C:10]#[N:11])[cH:23][c:24]([O:25][CH3:26])[c:27]1[O:28][CH3:29].[OH:12][c:13]1[cH:14][cH:15][cH:16][c:17]2[n:18][cH:19][cH:20][cH:21][c:22]12>>[CH3:1][O:2][c:3]1[cH:4][c:5]([CH:6]2[C:7]([C:8]#[N:9])=[C:10]([NH2:11])[O:12][c:13]3[c:14]2[cH:15][cH:16][c:17]2[n:18][c...
COc1cc(C=C(C#N)C#N)cc(OC)c1OC.Oc1cccc2ncccc12
COc1cc(C2C(C#N)=C(N)Oc3c2ccc2ncccc32)cc(OC)c1OC
null
null
null
Acylation
OtherReaction
ea8195ef7b92aa5adf18836e24efa2282d12f28bca1973edef107593961550ee
ddf492156ebbbd95b0675ccdaeb616c1c2acd58502f5ae6be273b2a40457d4ef
C1=CC(c2ccccc2)c2ccc3ncccc3c2O1
[#7;a:1]:[c:2]1:[c:3]:[c:4]:[cH;D2;+0:5]:[c:6](-[OH;D1;+0:7]):[c:8]:1.[N;D1;H0:9]#[C:10]-[C;H0;D3;+0:11](-[C;H0;D2;+0:12]#[N;H0;D1;+0:13])=[CH;D2;+0:14]-[c:15](:[c:16]):[c:17]>>[#7;a:1]:[c:2]1:[c:3]:[c:4]:[c;H0;D3;+0:5]2:[c:6](:[c:8]:1)-[O;H0;D2;+0:7]-[C;H0;D3;+0:12](-[NH2;D1;+0:13])=[C;H0;D3;+0:11](-[C:10]#[N;D1;H0:9]...
null
[]
null
null
null
null
The title compound was prepared from 3,4,5-trimethoxybenzylidenemalononitrile (244 mg, 1 mmol) and 5-hydroxyquinoline by a procedure similar to that described for Example 145.11H NMR (CDCl3): 8.96 (m, 1H), 8.52 (d, J=8.7, 1H), 7.82 (d, J=9.0, 1H), 7.52 (m, 1H), 7.33 (d, J=8.7, 1H), 6.43 (s, 2H), 4.83 (m, 3H), 3.83 (s, ...
10.6084/m9.figshare.5104873.v1
null
Nitrile.Aromatic alcohol
Enamine.Ether
c1ccc2ncccc2c1
C1=COc2c(ccc3ncccc23)C1
c1ccccc1.C1=COc2c(ccc3ncccc23)C1
null
null
null
null
COc1cc(C=C(C#N)C#N)cc(OC)c1OC.Oc1cccc2ncccc12>>COc1cc(C2C(C#N)=C(N)Oc3c2ccc2ncccc32)cc(OC)c1OC
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-dc32dab8144d4f6a9059963a3961787d
CN(C(=O)CCCCC(c1ccc(F)cc1)c1ccc(F)cc1)C1CCN(C(=O)c2ccccc2)C1>>CN(C(=O)CCCCC(c1ccc(F)cc1)c1ccc(F)cc1)[C@@H]1CCNC1
C(C1=CC=CC=C1)(=O)N1CC(CC1)N(C(CCCCC(C1=CC=C(C=C1)F)C1=CC=C(C=C1)F)=O)C>>CN(C(CCCCC(C1=CC=C(C=C1)F)C1=CC=C(C=C1)F)=O)[C@H]1CNCC1
O=C(c1ccccc1)[N:27]1[CH2:26][CH2:25][CH:24]([N:2]([CH3:1])[C:3](=[O:4])[CH2:5][CH2:6][CH2:7][CH2:8][CH:9]([c:10]2[cH:11][cH:12][c:13]([F:14])[cH:15][cH:16]2)[c:17]2[cH:18][cH:19][c:20]([F:21])[cH:22][cH:23]2)[CH2:28]1>>[CH3:1][N:2]([C:3](=[O:4])[CH2:5][CH2:6][CH2:7][CH2:8][CH:9]([c:10]1[cH:11][cH:12][c:13]([F:14])[cH:1...
CN(C(=O)CCCCC(c1ccc(F)cc1)c1ccc(F)cc1)C1CCN(C(=O)c2ccccc2)C1
CN(C(=O)CCCCC(c1ccc(F)cc1)c1ccc(F)cc1)[C@@H]1CCNC1
null
[Pd]
CO
Reduction
Hydrogenolysis of tertiary amines
f31a24fac1247652ffb9d16bd05f6451f460ef232d259564a837b8998ec61ef8
62cf08a8ae6315067a063b5b3495125ccbdaff6b2340ce1d3e1c7b6cde962ae4
O=C(CCCCC(c1ccccc1)c1ccccc1)N[C@@H]1CCNC1
O=C(-[N;H0;D3;+0:1]1-[C:2]-[C:3]-[C:4]-[C:5]-1)-c1:c:c:c:c:c:1>>[C:4]1-[C:3]-[C:2]-[NH;D2;+0:1]-[C:5]-1
null
[]
null
null
24
HOUR
To a solution of 6,6-Bis-(4-fluoro-phenyl)-hexanoic acid(1-benzoyl-pyrrolidin-3-yl)-methyl amide(1.0 g, 2.1 mmol in CH3OH (50 ml) was added Pd/C 20% (250 mg). The resulting slurry was hydrogenated at 50 psi for 24 hours. The catalyst was filtered through Celite and filtrate evaporated under reduced pressure to give 0.7...
10.6084/m9.figshare.5104873.v1
null
Tertiary amide
Secondary amine
c1ccccc1.C1CC[NH]C1
C1CCNC1
c1ccccc1.c1ccccc1.C1CCNC1
HO-
[Pd].CO
null
24
CN(C(=O)CCCCC(c1ccc(F)cc1)c1ccc(F)cc1)C1CCN(C(=O)c2ccccc2)C1>[Pd].CO>CN(C(=O)CCCCC(c1ccc(F)cc1)c1ccc(F)cc1)[C@@H]1CCNC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-f5d8b6a413cc454b9f8f119c04545da2
CN(C(=O)CCCCC(c1ccc(F)cc1)c1ccc(F)cc1)[C@@H]1CCNC1.COc1c(C(C)(C)C)cc(C(=O)O)cc1C(C)(C)C>>COc1c(C(C)(C)C)cc(C(=O)N2CC[C@@H](N(C)C(=O)CCCCC(c3ccc(F)cc3)c3ccc(F)cc3)C2)cc1C(C)(C)C
C(CCl)Cl.CN(C(CCCCC(C1=CC=C(C=C1)F)C1=CC=C(C=C1)F)=O)[C@H]1CNCC1.C(C)(C)(C)C=1C=C(C(=O)O)C=C(C1OC)C(C)(C)C>>C(C)(C)(C)C=1C=C(C(=O)N2C[C@@H](CC2)N(C(CCCCC(C2=CC=C(C=C2)F)C2=CC=C(C=C2)F)=O)C)C=C(C1OC)C(C)(C)C
[NH:13]1[CH2:14][CH2:15][C@@H:16]([N:17]([CH3:18])[C:19](=[O:20])[CH2:21][CH2:22][CH2:23][CH2:24][CH:25]([c:26]2[cH:27][cH:28][c:29]([F:30])[cH:31][cH:32]2)[c:33]2[cH:34][cH:35][c:36]([F:37])[cH:38][cH:39]2)[CH2:40]1.O[C:11]([c:10]1[cH:9][c:4]([C:5]([CH3:6])([CH3:7])[CH3:8])[c:3]([O:2][CH3:1])[c:42]([C:43]([CH3:44])([C...
CN(C(=O)CCCCC(c1ccc(F)cc1)c1ccc(F)cc1)[C@@H]1CCNC1.COc1c(C(C)(C)C)cc(C(=O)O)cc1C(C)(C)C
COc1c(C(C)(C)C)cc(C(=O)N2CC[C@@H](N(C)C(=O)CCCCC(c3ccc(F)cc3)c3ccc(F)cc3)C2)cc1C(C)(C)C
null
CN(C)C=1C=CN=CC1
C(Cl)Cl
Acylation
Acylation of Nitrogen Nucleophiles by Carboxylic Acids
a590d96426a2fbaed42913d9daf8a16471a16de4978200f1d35a30a10009ebe7
c5e4172490b2731ba9322b68af56376edadc31ce0bb9a3dfdea23a1817a852fd
O=C(CCCCC(c1ccccc1)c1ccccc1)N[C@@H]1CCN(C(=O)c2ccccc2)C1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C:6]1-[C:7]-[C:8]-[C:9]-[NH;D2;+0:10]-1>>[O;D1;H0:2]=[C;H0;D3;+0:1](-[N;H0;D3;+0:10]1-[C:6]-[C:7]-[C:8]-[C:9]-1)-[c:3](:[c:4]):[c:5]
86.1
[{"value": 86.1, "product": "C(C)(C)(C)C=1C=C(C(=O)N2C[C@@H](CC2)N(C(CCCCC(C2=CC=C(C=C2)F)C2=CC=C(C=C2)F)=O)C)C=C(C1OC)C(C)(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
To a solution of (R)-6,6-Bis-(4-fluoro-phenyl)-hexanoic acid methyl-pyrrolidin-3-yl-amide (0.78 g, 2.02 mmol) in dry CH2Cl2 (30 ml) was added 3,5-di-tert-butyl-4-methoxy benzoic acid (0.53 g, 2.02 mmol) under nitrogen. To the reaction was added EDC (0.77 g, 4.04 mmol) and DMAP (cat) and the reaction mixture stirred und...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Secondary amine
Tertiary amide
C1CCNC1
C1CC[NH]C1
c1ccccc1.C1CC[NH]C1.c1ccccc1.c1ccccc1
HO-
CN(C)C=1C=CN=CC1.C(Cl)Cl
null
8
CN(C(=O)CCCCC(c1ccc(F)cc1)c1ccc(F)cc1)[C@@H]1CCNC1.COc1c(C(C)(C)C)cc(C(=O)O)cc1C(C)(C)C>CN(C)C=1C=CN=CC1.C(Cl)Cl>COc1c(C(C)(C)C)cc(C(=O)N2CC[C@@H](N(C)C(=O)CCCCC(c3ccc(F)cc3)c3ccc(F)cc3)C2)cc1C(C)(C)C
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a3bd9ab8933c44248386fa66145baa8d
CN(C(=O)CC(c1ccccc1)c1ccccc1)C1CCNC1.O=Cc1ccncc1>>CN(C(=O)CC(c1ccccc1)c1ccccc1)[C@@H]1CCN(Cc2ccncc2)C1
CN(C(CC(C1=CC=CC=C1)C1=CC=CC=C1)=O)C1CNCC1.N1=CC=C(C=C1)C=O.C(C)(=O)O[BH-](OC(C)=O)OC(C)=O.[Na+]>>CN(C(CC(C1=CC=CC=C1)C1=CC=CC=C1)=O)[C@H]1CN(CC1)CC1=CC=NC=C1
[CH3:1][N:2]([C:3](=[O:4])[CH2:5][CH:6]([c:7]1[cH:8][cH:9][cH:10][cH:11][cH:12]1)[c:13]1[cH:14][cH:15][cH:16][cH:17][cH:18]1)[CH:19]1[CH2:20][CH2:21][NH:22][CH2:30]1.O=[CH:23][c:24]1[cH:25][cH:26][n:27][cH:28][cH:29]1>>[CH3:1][N:2]([C:3](=[O:4])[CH2:5][CH:6]([c:7]1[cH:8][cH:9][cH:10][cH:11][cH:12]1)[c:13]1[cH:14][cH:15...
CN(C(=O)CC(c1ccccc1)c1ccccc1)C1CCNC1.O=Cc1ccncc1
CN(C(=O)CC(c1ccccc1)c1ccccc1)[C@@H]1CCN(Cc2ccncc2)C1
null
null
C(Cl)Cl
Heteroatom Alkylation and Arylation
reductive amination
f320c54beea598cd731a01400cf9495fa26416685f3307ec69cb487e38cf79c3
2d03f38884b1fbb0c0d6e6f2de31afb25102fec87f347c3a123e064c1bfef0ad
O=C(CC(c1ccccc1)c1ccccc1)N[C@@H]1CCN(Cc2ccncc2)C1
O=[CH;D2;+0:1]-[c:2]1:[c:3]:[c:4]:[#7;a:5]:[c:6]:[c:7]:1.[C:8]1-[C:9]-[C:10]-[NH;D2;+0:11]-[C:12]-1>>[#7;a:5]1:[c:4]:[c:3]:[c:2](-[CH2;D2;+0:1]-[N;H0;D3;+0:11]2-[C:10]-[C:9]-[C:8]-[C:12]-2):[c:7]:[c:6]:1
null
[]
null
null
8
HOUR
To a solution of N-methyl-3,3-diphenyl-N-pyrrolidin-3-yl-propionamide(0.45 g, 1.46 mmol) in CH2Cl2 (10 ml) was added 4-pyridinecarboxaldehyde(0.14 ml, 1.46 mmol), sodium triacetoxyborohydride(0.4 g, 1.89 mmol) and ACOH (0.17 ml, 2.92 mmol). The resulting solution was stirred at room temperature under nitrogen overnight...
10.6084/m9.figshare.5104873.v1
null
Aldehyde.Secondary amine
Tertiary amine
C1CCNC1
C1CC[NH]C1
c1ccccc1.c1ccccc1.C1CC[NH]C1.c1ccncc1
Other
C(Cl)Cl
null
8
CN(C(=O)CC(c1ccccc1)c1ccccc1)C1CCNC1.O=Cc1ccncc1>C(Cl)Cl>CN(C(=O)CC(c1ccccc1)c1ccccc1)[C@@H]1CCN(Cc2ccncc2)C1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-4b9b104873a24f28b297fe2e3acb4c52
CN[C@@H]1CCN(C(=O)c2ccccc2)C1.O=C=NC(c1ccccc1)c1ccccc1>>CN(C(=O)NC(c1ccccc1)c1ccccc1)[C@@H]1CCN(Cc2ccccc2)C1
C(C1=CC=CC=C1)(=O)N1C[C@@H](CC1)NC.C1(=CC=CC=C1)C(C1=CC=CC=C1)N=C=O>>C(C1=CC=CC=C1)(C1=CC=CC=C1)NC(N(C)[C@H]1CN(CC1)CC1=CC=CC=C1)=O
O=[C:23]([N:22]1[CH2:21][CH2:20][C@@H:19]([NH:2][CH3:1])[CH2:30]1)[c:24]1[cH:25][cH:26][cH:27][cH:28][cH:29]1.[C:3](=[O:4])=[N:5][CH:6]([c:7]1[cH:8][cH:9][cH:10][cH:11][cH:12]1)[c:13]1[cH:14][cH:15][cH:16][cH:17][cH:18]1>>[CH3:1][N:2]([C:3](=[O:4])[NH:5][CH:6]([c:7]1[cH:8][cH:9][cH:10][cH:11][cH:12]1)[c:13]1[cH:14][cH:...
CN[C@@H]1CCN(C(=O)c2ccccc2)C1.O=C=NC(c1ccccc1)c1ccccc1
CN(C(=O)NC(c1ccccc1)c1ccccc1)[C@@H]1CCN(Cc2ccccc2)C1
null
null
C(Cl)Cl
Acylation
OtherReaction
74260046603649fc395e9d3c55a57d192ab3ac71476c8cd70621864058712e96
626f1d479955946092959f41e51d9bd68cb2ca1088930412532e655b2a1d7d80
O=C(NC(c1ccccc1)c1ccccc1)N[C@@H]1CCN(Cc2ccccc2)C1
O=[C;H0;D3;+0:1](-[#7:2]1-[C:3]-[C:4]-[C:5](-[NH;D2;+0:6]-[C;D1;H3:7])-[C:8]-1)-[c:9](:[c:10]):[c:11].[O;D1;H0:12]=[C;H0;D2;+0:13]=[N;H0;D2;+0:14]-[C:15](-[c:16])-[c:17]>>[C;D1;H3:7]-[N;H0;D3;+0:6](-[C:5]1-[C:4]-[C:3]-[#7:2](-[CH2;D2;+0:1]-[c:9](:[c:10]):[c:11])-[C:8]-1)-[C;H0;D3;+0:13](=[O;D1;H0:12])-[NH;D2;+0:14]-[C:...
96.8
[{"value": 96.8, "product": "C(C1=CC=CC=C1)(C1=CC=CC=C1)NC(N(C)[C@H]1CN(CC1)CC1=CC=CC=C1)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
To a solution of (R)-(1-benzoyl-pyrrolidin-3-yl)-methyl-amine(0.32 g, 1.68 mmol) in dry CH2Cl2 (5 ml) was added diphenylmethyl isocyanate(0.32 ml, 1.68 mmol) dropwise under nitrogen. The resulting mixture was stirred at room temperature overnight. Removal of solvent under reduced pressure followed by column chromatogra...
10.6084/m9.figshare.5104873.v1
null
Isocyanate.Tertiary amide.Secondary amine
Urea
null
null
c1ccccc1.c1ccccc1.C1CC[NH]C1.c1ccccc1
Other
C(Cl)Cl
null
8
CN[C@@H]1CCN(C(=O)c2ccccc2)C1.O=C=NC(c1ccccc1)c1ccccc1>C(Cl)Cl>CN(C(=O)NC(c1ccccc1)c1ccccc1)[C@@H]1CCN(Cc2ccccc2)C1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-189f5f3cf8bb43dca2e6b5ca20960bd3
CN(C(=O)NC(c1ccccc1)c1ccccc1)C1CCN(C(=O)c2ccccc2)C1>>CN(C(=O)NC(c1ccccc1)c1ccccc1)[C@@H]1CCNC1
C(C1=CC=CC=C1)(C1=CC=CC=C1)NC(N(C)C1CN(CC1)C(C1=CC=CC=C1)=O)=O>>C(C1=CC=CC=C1)(C1=CC=CC=C1)NC(N([C@H]1CNCC1)C)=O
O=C(c1ccccc1)[N:22]1[CH2:21][CH2:20][CH:19]([N:2]([CH3:1])[C:3](=[O:4])[NH:5][CH:6]([c:7]2[cH:8][cH:9][cH:10][cH:11][cH:12]2)[c:13]2[cH:14][cH:15][cH:16][cH:17][cH:18]2)[CH2:23]1>>[CH3:1][N:2]([C:3](=[O:4])[NH:5][CH:6]([c:7]1[cH:8][cH:9][cH:10][cH:11][cH:12]1)[c:13]1[cH:14][cH:15][cH:16][cH:17][cH:18]1)[C@@H:19]1[CH2:2...
CN(C(=O)NC(c1ccccc1)c1ccccc1)C1CCN(C(=O)c2ccccc2)C1
CN(C(=O)NC(c1ccccc1)c1ccccc1)[C@@H]1CCNC1
null
[Pd]
CO
Reduction
Hydrogenolysis of tertiary amines
f31a24fac1247652ffb9d16bd05f6451f460ef232d259564a837b8998ec61ef8
62cf08a8ae6315067a063b5b3495125ccbdaff6b2340ce1d3e1c7b6cde962ae4
O=C(NC(c1ccccc1)c1ccccc1)N[C@@H]1CCNC1
O=C(-[N;H0;D3;+0:1]1-[C:2]-[C:3]-[C:4]-[C:5]-1)-c1:c:c:c:c:c:1>>[C:4]1-[C:3]-[C:2]-[NH;D2;+0:1]-[C:5]-1
116.4
[{"value": 116.4, "product": "C(C1=CC=CC=C1)(C1=CC=CC=C1)NC(N([C@H]1CNCC1)C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
24
HOUR
To a solution of 3-benzhydryl-1-(1-benzoyl-pyrrolidin-3-yl)-1-methyl-urea (0.7 g, 1.75 mmol) in CH3OH (25 ml) was added Pd/C 20% (175 mg). The resulting slurry was hydrogenated at 50 psi for 24 hours. The catalyst was filtered through Celite and filtrate evaporated under reduced pressure to, give 0.63 g of desired prod...
10.6084/m9.figshare.5104873.v1
null
Tertiary amide
Secondary amine
c1ccccc1.C1CC[NH]C1
C1CCNC1
c1ccccc1.c1ccccc1.C1CCNC1
HO-
[Pd].CO
null
24
CN(C(=O)NC(c1ccccc1)c1ccccc1)C1CCN(C(=O)c2ccccc2)C1>[Pd].CO>CN(C(=O)NC(c1ccccc1)c1ccccc1)[C@@H]1CCNC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-64ad327fd7e5418c8db679f5c0b209c6
BrC(c1ccccc1)c1ccccc1.CN(C(=O)NC(c1ccccc1)c1ccccc1)C1CCNC1>>CN(C(=O)NC(c1ccccc1)c1ccccc1)[C@@H]1CCN(C(c2ccccc2)c2ccccc2)C1
BrC(C1=CC=CC=C1)C1=CC=CC=C1.C(C1=CC=CC=C1)(C1=CC=CC=C1)NC(N(C1CNCC1)C)=O.C(=O)([O-])[O-].[K+].[K+]>>C(C1=CC=CC=C1)(C1=CC=CC=C1)NC(N(C)[C@H]1CN(CC1)C(C1=CC=CC=C1)C1=CC=CC=C1)=O
Br[CH:23]([c:24]1[cH:25][cH:26][cH:27][cH:28][cH:29]1)[c:30]1[cH:31][cH:32][cH:33][cH:34][cH:35]1.[CH3:1][N:2]([C:3](=[O:4])[NH:5][CH:6]([c:7]1[cH:8][cH:9][cH:10][cH:11][cH:12]1)[c:13]1[cH:14][cH:15][cH:16][cH:17][cH:18]1)[CH:19]1[CH2:20][CH2:21][NH:22][CH2:36]1>>[CH3:1][N:2]([C:3](=[O:4])[NH:5][CH:6]([c:7]1[cH:8][cH:9...
BrC(c1ccccc1)c1ccccc1.CN(C(=O)NC(c1ccccc1)c1ccccc1)C1CCNC1
CN(C(=O)NC(c1ccccc1)c1ccccc1)[C@@H]1CCN(C(c2ccccc2)c2ccccc2)C1
null
null
CC(CC)=O
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
10cc789bcfe0ae11c7b2b474c79d3cdda850354ad720004a77dedb66c0fbd515
fb63ba09935e18320be03869002f6d5d0f0321fe7dbcd94a5ae956c3effd182d
O=C(NC(c1ccccc1)c1ccccc1)N[C@@H]1CCN(C(c2ccccc2)c2ccccc2)C1
Br-[CH;D3;+0:1](-[c:2](:[c:3]):[c:4])-[c:5](:[c:6]):[c:7].[C:8]1-[C:9]-[C:10]-[NH;D2;+0:11]-[C:12]-1>>[c:3]:[c:2](-[CH;D3;+0:1](-[N;H0;D3;+0:11]1-[C:10]-[C:9]-[C:8]-[C:12]-1)-[c:5](:[c:6]):[c:7]):[c:4]
null
[]
null
null
null
null
To a solution of bromodiphenylmethane (0.43 g, 1.75 mmol) in butanone (10 ml) was added 3-benzhydryl-1-methyl-1-pyrrolidin-3-yl-urea(0.65 g, 2.1 mmol), K2CO3 (0.24, 1.75 mmol) and KI (0.29 g, 1.75 mmol). The mixture was heated under reflux for 18 hours, then filtered and the solvent was removed in vacuo. The residue wa...
10.6084/m9.figshare.5104873.v1
null
Secondary halide.Secondary amine
Tertiary amine
C1CCNC1
C1CC[NH]C1
c1ccccc1.c1ccccc1.C1CC[NH]C1.c1ccccc1.c1ccccc1
HBr
CC(CC)=O
null
null
BrC(c1ccccc1)c1ccccc1.CN(C(=O)NC(c1ccccc1)c1ccccc1)C1CCNC1>CC(CC)=O>CN(C(=O)NC(c1ccccc1)c1ccccc1)[C@@H]1CCN(C(c2ccccc2)c2ccccc2)C1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-fa9c619af59e4c759fc0932583cffe39
CN[C@@H]1CCN(C(=O)c2ccccc2)C1.O=C(O)CN(c1ccccc1)c1ccccc1>>CN(C(=O)CN(c1ccccc1)c1ccccc1)[C@@H]1CCN(Cc2ccccc2)C1
C(CCl)Cl.C(C1=CC=CC=C1)(=O)N1C[C@@H](CC1)NC.C1(=CC=CC=C1)N(C1=CC=CC=C1)CC(=O)O>>C(C1=CC=CC=C1)N1C[C@@H](CC1)N(C(CN(C1=CC=CC=C1)C1=CC=CC=C1)=O)C
O=[C:23]([N:22]1[CH2:21][CH2:20][C@@H:19]([NH:2][CH3:1])[CH2:30]1)[c:24]1[cH:25][cH:26][cH:27][cH:28][cH:29]1.O[C:3](=[O:4])[CH2:5][N:6]([c:7]1[cH:8][cH:9][cH:10][cH:11][cH:12]1)[c:13]1[cH:14][cH:15][cH:16][cH:17][cH:18]1>>[CH3:1][N:2]([C:3](=[O:4])[CH2:5][N:6]([c:7]1[cH:8][cH:9][cH:10][cH:11][cH:12]1)[c:13]1[cH:14][cH...
CN[C@@H]1CCN(C(=O)c2ccccc2)C1.O=C(O)CN(c1ccccc1)c1ccccc1
CN(C(=O)CN(c1ccccc1)c1ccccc1)[C@@H]1CCN(Cc2ccccc2)C1
null
CN(C)C=1C=CN=CC1
C(Cl)Cl
Acylation
OtherReaction
54b269d0f28fb1926d29899001218d7b6cda7f176425e41c60d8cf23ca5b9e74
66c584447dc5daff0aa8fe93aecae17349beecb2ac876e4bae5adb72d01b4bc0
O=C(CN(c1ccccc1)c1ccccc1)N[C@@H]1CCN(Cc2ccccc2)C1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[#7:4].O=[C;H0;D3;+0:5](-[#7:6]1-[C:7]-[C:8]-[C:9](-[NH;D2;+0:10]-[C;D1;H3:11])-[C:12]-1)-[c:13](:[c:14]):[c:15]>>[#7:4]-[C:3]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[N;H0;D3;+0:10](-[C;D1;H3:11])-[C:9]1-[C:8]-[C:7]-[#7:6](-[CH2;D2;+0:5]-[c:13](:[c:14]):[c:15])-[C:12]-1
101.3
[{"value": 101.3, "product": "C(C1=CC=CC=C1)N1C[C@@H](CC1)N(C(CN(C1=CC=CC=C1)C1=CC=CC=C1)=O)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
To a solution of (R)-(1-benzoyl-pyrrolidin-3-yl)-methyl-amine(0.32 g, 1.68 mmol) in dry CH2Cl2 (20 ml) was added diphenylaminoacetic acid (0.38 g, 1.68 mmol) under nitrogen. To the reaction was added EDC (0.65 g, 3.36 mmol) and DMAP (cat) and the reaction mixture stirred under nitrogen at room temperature overnight. Th...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Tertiary amide.Secondary amine
Tertiary amide
null
null
c1ccccc1.c1ccccc1.C1CC[NH]C1.c1ccccc1
Other
CN(C)C=1C=CN=CC1.C(Cl)Cl
null
8
CN[C@@H]1CCN(C(=O)c2ccccc2)C1.O=C(O)CN(c1ccccc1)c1ccccc1>CN(C)C=1C=CN=CC1.C(Cl)Cl>CN(C(=O)CN(c1ccccc1)c1ccccc1)[C@@H]1CCN(Cc2ccccc2)C1