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-018fd0e1351f4fd09b20fcddd97b4c7a
ord-2530436b50534fbdbbf72c2ea6ad27e3
Cc1cc([N+](=O)[O-])cnc1Cl.[F-]>>Cc1cc([N+](=O)[O-])cnc1F
ClC1=NC=C(C=C1C)[N+](=O)[O-].[F-].[K+]>>FC1=NC=C(C=C1C)[N+](=O)[O-]
Cl[c:10]1[c:2]([CH3:1])[cH:3][c:4]([N+:5](=[O:6])[O-:7])[cH:8][n:9]1.[F-:11]>>[CH3:1][c:2]1[cH:3][c:4]([N+:5](=[O:6])[O-:7])[cH:8][n:9][c:10]1[F:11]
Cc1cc([N+](=O)[O-])cnc1Cl.[F-]
Cc1cc([N+](=O)[O-])cnc1F
null
[Br-].C1(=CC=CC=C1)[P+](C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1
C(C)#N.CCOCC
Functional Group Interconversion
OtherReaction
c5ee9801df82c43b4536f3b3bcf4d5fc4f4f88678c4231db54140fcd8ba626c5
4131cd1655d0ec8ecf7e181a36ab37eb3293d734e38ece0acf0e59405d170401
c1ccncc1
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[c:4](-[C;D1;H3:5]):[c:6].[F-;H0;D0:7]>>[C;D1;H3:5]-[c:4](:[c:6]):[c;H0;D3;+0:1](-[F;H0;D1;+0:7]):[#7;a:2]:[c:3]
61.9
[{"value": 60.0, "product": "FC1=NC=C(C=C1C)[N+](=O)[O-]", "details": "PERCENTYIELD", "is_desired": false}, {"value": 61.9, "product": "FC1=NC=C(C=C1C)[N+](=O)[O-]", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
2-Chloro-3-methyl-5-nitropyridine (15 g, 86.9 mmol; from Maybridge Chemical Co.), KF (12 g, 258 mmol) and tetraphenylphosphonium bromide (20 g, 47.7 mmol; Aldrich) were combined in 200 mL of acetonitrile and heated at reflux for 4 days. The mixture was diluted with Et2O (500 mL) and filtered, and the filtrate was conce...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
Aromatic halide
c1ccncc1
c1ccncc1
c1ccncc1
Other
[Br-].C1(=CC=CC=C1)[P+](C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1.C(C)#N.CCOCC
null
null
Cc1cc([N+](=O)[O-])cnc1Cl.[F-]>[Br-].C1(=CC=CC=C1)[P+](C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1.C(C)#N.CCOCC>Cc1cc([N+](=O)[O-])cnc1F
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-8caea27682284e0fa725f4c5568af18a
Cc1cc([N+](=O)[O-])cnc1F>>Cc1cc(N)cnc1F
FC1=NC=C(C=C1C)[N+](=O)[O-]>>NC=1C=C(C(=NC1)F)C
O=[N+:5]([O-])[c:4]1[cH:3][c:2]([CH3:1])[c:8]([F:9])[n:7][cH:6]1>>[CH3:1][c:2]1[cH:3][c:4]([NH2:5])[cH:6][n:7][c:8]1[F:9]
Cc1cc([N+](=O)[O-])cnc1F
Cc1cc(N)cnc1F
null
[Pd]
CCO
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
c1ccncc1
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]:[#7;a:5]:[c:6]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]:[#7;a:5]:[c:6]
78.5
[{"value": 78.0, "product": "NC=1C=C(C(=NC1)F)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 78.5, "product": "NC=1C=C(C(=NC1)F)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
2-Fluoro-3-methyl-5-nitropyridine (8.2 g, mmol) was combined with 5% Pd/C (100 mg) in EtOH (100 mL) under a H2 atmosphere for 16 hours. The mixture was filtered and concentrated, and the crude product was chromatographed (silica gel; CHCl3 /MeOH 99:1 to 96:4) to afford a solid (5.2 g, 78% ): 1H NMR (DMSO-d6, 300 MHz) δ...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1ccncc1
Other
[Pd].CCO
null
null
Cc1cc([N+](=O)[O-])cnc1F>[Pd].CCO>Cc1cc(N)cnc1F
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-b6a3efbece064552a88a0a3c4985d4a0
C1CC2=[N+](C1)CCC2.Cc1cc(I)cnc1F>>Cc1cc(C23CCCN2CCC3)cnc1F
FC1=NC=C(C=C1C)I.[Li]C(C)(C)C.Cl(=O)(=O)(=O)[O-].C1CC[N+]=2CCCC12>>FC1=C(C=C(C=N1)C12CCCN2CCC1)C
[C:5]12=[N+:9]([CH2:8][CH2:7][CH2:6]1)[CH2:10][CH2:11][CH2:12]2.I[c:4]1[cH:3][c:2]([CH3:1])[c:15]([F:16])[n:14][cH:13]1>>[CH3:1][c:2]1[cH:3][c:4]([C:5]23[CH2:6][CH2:7][CH2:8][N:9]2[CH2:10][CH2:11][CH2:12]3)[cH:13][n:14][c:15]1[F:16]
C1CC2=[N+](C1)CCC2.Cc1cc(I)cnc1F
Cc1cc(C23CCCN2CCC3)cnc1F
null
null
CCCCC.CCOCC
Functional Group Interconversion
OtherReaction
6e757ff9396a07e923211312afac1c080dd23eff3444ff9c846ed5fe9d4243b6
773dbb8365a8bceadef31887b9f43d5f4f5443038ea5ede92ac6bcd66c5d17b4
c1cncc(C23CCCN2CCC3)c1
I-[c;H0;D3;+0:1]1:[c:2]:[#7;a:3]:[c:4]:[c:5]:[c:6]:1.[C:7]1-[C:8]-[C:9]-[C;H0;D3;+0:10]2=[N+;H0;D3:11]-1-[C:12]-[C:13]-[C:14]-2>>[#7;a:3]1:[c:2]:[c;H0;D3;+0:1](-[C;H0;D4;+0:10]23-[C:9]-[C:8]-[C:7]-[N;H0;D3;+0:11]-2-[C:12]-[C:13]-[C:14]-3):[c:6]:[c:5]:[c:4]:1
67
[{"value": 67.0, "product": "FC1=C(C=C(C=N1)C12CCCN2CCC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 66.5, "product": "FC1=C(C=C(C=N1)C12CCCN2CCC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
-95
CELSIUS
2
HOUR
2-Fluoro-5-iodo-3-methylpyridine (200 mg, 0.84 mmol) was dissolved in Et2O and cooled to -95° C. A solution of 2.5M t-BuLi (1.7M in pentane, 1.1 mL, 1.80 mmol) in pentane was added dropwise. 1,2,3,5,6,7-hexahydropyrrolizinium perchlorate (265 mg, 1.26 mmol) was added, and the reaction mixture was allowed to warm to -10...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
Tertiary amine
C1CC2=[N+](C1)CCC2.c1ccncc1
c1ccncc1.C1CC2CCCN2C1
c1ccncc1.C1CC2CCCN2C1
I-
CCCCC.CCOCC
-95
2
C1CC2=[N+](C1)CCC2.Cc1cc(I)cnc1F>CCCCC.CCOCC>Cc1cc(C23CCCN2CCC3)cnc1F
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-457e5f8be8b3495ea5aaa4132c8195ea
Cl>>Cl
Cl.FC1=C(C=C(C=N1)C12CCCN2CCC1)C>>Cl.FC1=C(C=C(C=N1)C12CCCN2CCC1)C
[ClH:17]>>[ClH:17]
Cl
Cl
null
null
CCOCC
Miscellaneous
OtherReaction
40ba59785861b8226ce5af6bdcbb9a37f0ff50a8c7ec7d4fc4c524cf906cc65c
56ebed4a8b3cebec83c37a71d68f0c87d1e404ab05a9ce792691e4e18a2379dd
null
null
69
[{"value": 69.0, "product": "Cl.FC1=C(C=C(C=N1)C12CCCN2CCC1)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
7a-(6-Fluoro-5-methyl-3-pyridinyl)-hexahydro-1H-pyrrolizine (115 mg, 0.52 mmol, from step 18d) was dissolved in Et2O, and Et2O saturated with HCl (g) was added. The solvent was removed, and the solid was crystallized from MeOH/Et2O and dried to afford the title compound (white needles, 92 mg, 69%): mp 170-171° C.; 1H N...
10.6084/m9.figshare.5104873.v1
null
null
null
null
null
null
null
CCOCC
null
null
Cl>CCOCC>Cl
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-fb181b43b2cf48a49bb845d00e4222a4
Cc1cc([N+](=O)[O-])cnc1Cl>>Cc1cc(N)cnc1Cl
ClC1=NC=C(C=C1C)[N+](=O)[O-]>>NC=1C=C(C(=NC1)Cl)C
O=[N+:5]([O-])[c:4]1[cH:3][c:2]([CH3:1])[c:8]([Cl:9])[n:7][cH:6]1>>[CH3:1][c:2]1[cH:3][c:4]([NH2:5])[cH:6][n:7][c:8]1[Cl:9]
Cc1cc([N+](=O)[O-])cnc1Cl
Cc1cc(N)cnc1Cl
null
[Fe]
O.CC(=O)O
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
c1ccncc1
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]:[#7;a:5]:[c:6]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]:[#7;a:5]:[c:6]
89
[{"value": 89.0, "product": "NC=1C=C(C(=NC1)Cl)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 18.6, "product": "NC=1C=C(C(=NC1)Cl)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
5
HOUR
2-Chloro-3-methyl-5-nitropyridine (15 g, 86.9 mmol; from Maybridge Chemical Co.) was dissolved in a solution of H2O/AcOH (5:1, 60 mL). Iron powder was added to the reaction mixture while maintaining the temperature below 40° C., and the mixture was stirred for 5 hours. The mixture was filtered through celite and the aq...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1ccncc1
Other
[Fe].O.CC(=O)O
null
5
Cc1cc([N+](=O)[O-])cnc1Cl>[Fe].O.CC(=O)O>Cc1cc(N)cnc1Cl
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-b41b8bae64dd42eb82a4b840e4ce0359
Cl>>Cl
Cl.ClC1=C(C=C(C=N1)C12CCCN2CCC1)C>>Cl.ClC1=C(C=C(C=N1)C12CCCN2CCC1)C
[ClH:17]>>[ClH:17]
Cl
Cl
null
null
CCOCC
Miscellaneous
OtherReaction
40ba59785861b8226ce5af6bdcbb9a37f0ff50a8c7ec7d4fc4c524cf906cc65c
56ebed4a8b3cebec83c37a71d68f0c87d1e404ab05a9ce792691e4e18a2379dd
null
null
null
[]
null
null
null
null
7a-(6-Chloro-5-methyl-3-pyridinyl)-hexahydro-1H-pyrrolizine (245 mg, 1.03 mmol) was dissolved in Et2O, and Et2O saturated with HCl (g) was added. The solvent was removed, and the solid was crystallized from MeOH/Et2O and dried to afford the title compound as white plates: mp 179°-180° C.; 1H NMR D2O, 300 MHz) δ2.14-2.4...
10.6084/m9.figshare.5104873.v1
null
null
null
null
null
null
null
CCOCC
null
null
Cl>CCOCC>Cl
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-25297c07e8f0461b9c58636fbdf6865e
C1CC2=[N+](C1)CCC2.Cc1ccc(I)cn1>>Cc1ccc(C23CCCN2CCC3)cn1
IC=1C=CC(=NC1)C.[Li]C(C)(C)C.Cl(=O)(=O)(=O)[O-].C1CC[N+]=2CCCC12>>CC1=CC=C(C=N1)C12CCCN2CCC1
[C:6]12=[N+:10]([CH2:9][CH2:8][CH2:7]1)[CH2:11][CH2:12][CH2:13]2.I[c:5]1[cH:4][cH:3][c:2]([CH3:1])[n:15][cH:14]1>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([C:6]23[CH2:7][CH2:8][CH2:9][N:10]2[CH2:11][CH2:12][CH2:13]3)[cH:14][n:15]1
C1CC2=[N+](C1)CCC2.Cc1ccc(I)cn1
Cc1ccc(C23CCCN2CCC3)cn1
null
null
CCCCC.CCOCC
Functional Group Interconversion
OtherReaction
6e757ff9396a07e923211312afac1c080dd23eff3444ff9c846ed5fe9d4243b6
773dbb8365a8bceadef31887b9f43d5f4f5443038ea5ede92ac6bcd66c5d17b4
c1cncc(C23CCCN2CCC3)c1
I-[c;H0;D3;+0:1]1:[c:2]:[#7;a:3]:[c:4]:[c:5]:[c:6]:1.[C:7]1-[C:8]-[C:9]-[C;H0;D3;+0:10]2=[N+;H0;D3:11]-1-[C:12]-[C:13]-[C:14]-2>>[#7;a:3]1:[c:2]:[c;H0;D3;+0:1](-[C;H0;D4;+0:10]23-[C:9]-[C:8]-[C:7]-[N;H0;D3;+0:11]-2-[C:12]-[C:13]-[C:14]-3):[c:6]:[c:5]:[c:4]:1
45
[{"value": 45.0, "product": "CC1=CC=C(C=N1)C12CCCN2CCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 44.8, "product": "CC1=CC=C(C=N1)C12CCCN2CCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
-95
CELSIUS
2
HOUR
5-Iodo-2-methylpyridine (345 mg, 1.39 mmol) was dissolved in Et2O and cooled to -95° C. A solution of 2.5M t-BuLi (1.7M in pentane, 1.8 mL, 3.06 mmol) in pentane was added dropwise. 1,2,3,5,6,7-hexahydropyrrolizinium perchlorate (435 mg, 2.1 mmol) was added, and the reaction mixture was allowed to warm to -10° C. with ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
Tertiary amine
C1CC2=[N+](C1)CCC2.c1ccncc1
c1ccncc1.C1CC2CCCN2C1
c1ccncc1.C1CC2CCCN2C1
I-
CCCCC.CCOCC
-95
2
C1CC2=[N+](C1)CCC2.Cc1ccc(I)cn1>CCCCC.CCOCC>Cc1ccc(C23CCCN2CCC3)cn1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-ea2e0597cfc34b5fb0309e1466c6a737
Cl>>Cl.Cl
Cl.CC1=CC=C(C=N1)C12CCCN2CCC1>>Cl.Cl.CC1=CC=C(C=N1)C12CCCN2CCC1
[ClH:16]>>[ClH:16].[ClH:17]
Cl
Cl.Cl
null
null
CCOCC
Miscellaneous
OtherReaction
40ba59785861b8226ce5af6bdcbb9a37f0ff50a8c7ec7d4fc4c524cf906cc65c
56ebed4a8b3cebec83c37a71d68f0c87d1e404ab05a9ce792691e4e18a2379dd
null
null
null
[]
null
null
null
null
7a-(6-methyl-3-pyridinyl)-hexahydro-1H-pyrrolizine (115 mg, 0.57 mmol) was dissolved in Et2O, and Et2O saturated with HCl (g) was added. The solvent was removed, and the solid was crystallized from MeOH/Et2O and dried to afford the title compound as a free flowing white powder: mp 205°-208° C.; 1H NMR D2O, 300 MHz) δ2....
10.6084/m9.figshare.5104873.v1
null
null
null
null
null
null
Other
CCOCC
null
null
Cl>CCOCC>Cl.Cl
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-e9f462982753453bbfd8fa8e28ec7c0c
Cc1cc(C23CCCN2CCC3)cnc1Cl>>Cc1cncc(C23CCCN2CCC3)c1
[H-].[H-].[H-].[H-].[Li+].[Al+3].ClC1=C(C=C(C=N1)C12CCCN2CCC1)C.[H-].[H-].[H-].[H-].[Li+].[Al+3].[H-].[H-].[H-].[H-].[Li+].[Al+3]>>CC=1C=C(C=NC1)C12CCCN2CCC1
Cl[c:3]1[c:2]([CH3:1])[cH:15][c:6]([C:7]23[CH2:8][CH2:9][CH2:10][N:11]2[CH2:12][CH2:13][CH2:14]3)[cH:5][n:4]1>>[CH3:1][c:2]1[cH:3][n:4][cH:5][c:6]([C:7]23[CH2:8][CH2:9][CH2:10][N:11]2[CH2:12][CH2:13][CH2:14]3)[cH:15]1
Cc1cc(C23CCCN2CCC3)cnc1Cl
Cc1cncc(C23CCCN2CCC3)c1
null
null
C1CCOC1
Functional Group Interconversion
Aromatic dehalogenation
ea85ec2fde5700c76b45764563e70d433b50e38e1af4209f646f155266c8ec96
56de34d4a44cb25d9380269ee5e138b0f24b40a3a0db22c5508049dc775a861f
c1cncc(C23CCCN2CCC3)c1
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[c:4](-[C;D1;H3:5]):[c:6]>>[C;D1;H3:5]-[c:4](:[c:6]):[cH;D2;+0:1]:[#7;a:2]:[c:3]
49.4
[{"value": 49.0, "product": "CC=1C=C(C=NC1)C12CCCN2CCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 49.4, "product": "CC=1C=C(C=NC1)C12CCCN2CCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
4
HOUR
7a-(6-Chloro-5-methyl-3-pyridinyl)-hexahydro-1H-pyrrolizine (274 mg, 1.16 mmol, from Example 19c) and LAH (1.0M in THF, 1.2 mL, 1.16 mmol) were added to THF (4.5 mL), and the mixture was stirred at room temperature for 4 hours. An additional amount of LAH (1.0M in THF, 1.2 mL, 1.16 mmol) was added, and the reaction was...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
null
c1ccncc1
c1ccncc1
c1ccncc1.C1CC2CCCN2C1
Other
C1CCOC1
null
4
Cc1cc(C23CCCN2CCC3)cnc1Cl>C1CCOC1>Cc1cncc(C23CCCN2CCC3)c1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-4307238908404aba91158ac3e78330d3
Cl>>Cl
Cl.CC=1C=C(C=NC1)C12CCCN2CCC1>>Cl.CC=1C=C(C=NC1)C12CCCN2CCC1
[ClH:16]>>[ClH:16]
Cl
Cl
null
null
CCOCC
Miscellaneous
OtherReaction
40ba59785861b8226ce5af6bdcbb9a37f0ff50a8c7ec7d4fc4c524cf906cc65c
56ebed4a8b3cebec83c37a71d68f0c87d1e404ab05a9ce792691e4e18a2379dd
null
null
87
[{"value": 87.0, "product": "Cl.CC=1C=C(C=NC1)C12CCCN2CCC1", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
7a-(5-methyl-3-pyridinyl)-hexahydro-1H-pyrrolizine (109 mg, 0.54 mmol) was dissolved in Et2O, and Et2O saturated with HCl (g) was added. The solvent was removed, and the solid was triturated with Et2O and dried to afford the title compound as a white powder (112 mg, 87%); mp 153°-154° C.; 1H NMR D2O, 300 MHz) δ2.12-2.4...
10.6084/m9.figshare.5104873.v1
null
null
null
null
null
null
null
CCOCC
null
null
Cl>CCOCC>Cl
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-ac9c0ef6fceb47cd8829f6fc3aa7a252
FC(F)(Br)C(F)(F)Br.Fc1ccc(C23CCCN2CCC3)cn1>>Fc1ncc(C23CCCN2CCC3)cc1Br
[Li]CCCC.C(C)(C)NC(C)C.FC1=CC=C(C=N1)C12CCCN2CCC1.BrC(C(F)(F)Br)(F)F>>BrC=1C=C(C=NC1F)C12CCCN2CCC1
FC(F)(Br)C(F)(F)[Br:16].[F:1][c:2]1[n:3][cH:4][c:5]([C:6]23[CH2:7][CH2:8][CH2:9][N:10]2[CH2:11][CH2:12][CH2:13]3)[cH:14][cH:15]1>>[F:1][c:2]1[n:3][cH:4][c:5]([C:6]23[CH2:7][CH2:8][CH2:9][N:10]2[CH2:11][CH2:12][CH2:13]3)[cH:14][c:15]1[Br:16]
FC(F)(Br)C(F)(F)Br.Fc1ccc(C23CCCN2CCC3)cn1
Fc1ncc(C23CCCN2CCC3)cc1Br
null
null
C1CCOC1
Functional Group Interconversion
Bromination
3dc3f72be681445c7fd24ed7b03fe65530bdb1cf64ea351f6f33b0039b7c8253
019ad5fd0dfe62cfb4244afde83961e2345586820445df7561489ed4a5d090fa
c1cncc(C23CCCN2CCC3)c1
Br-C(-F)(-F)-C(-F)(-F)-[Br;H0;D1;+0:1].[F;D1;H0:2]-[c:3]1:[#7;a:4]:[c:5]:[c:6]:[c:7]:[cH;D2;+0:8]:1>>[Br;H0;D1;+0:1]-[c;H0;D3;+0:8]1:[c:7]:[c:6]:[c:5]:[#7;a:4]:[c:3]:1-[F;D1;H0:2]
37.4
[{"value": 37.0, "product": "BrC=1C=C(C=NC1F)C12CCCN2CCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 37.4, "product": "BrC=1C=C(C=NC1F)C12CCCN2CCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
10
MINUTE
n-BuLi (2.5M in hexanes, 0.252 mL, 0.63 mmol) was added to di-isopropylamine (0.082 mL, 0.63 mmol) in THF and stirred at room temperature for 10 minutes, then cooled to -78° C. 7a-(6-Fluoro-3-pyridinyl)-hexahydro-1H-pyrrolizine (123 mg, 0.60 mmol, from Example 12d) and 1,2-dibromo-1,1,2,2-tetrafluoroethane (0.215 mL, 1...
10.6084/m9.figshare.5104873.v1
null
Tertiary halide.Tertiary halide.Tertiary halide.Tertiary halide.Tertiary halide.Tertiary halide
Aromatic halide
c1ccncc1
c1ccncc1
c1ccncc1.C1CC2CCCN2C1
HF.Br-
C1CCOC1
null
0.166667
FC(F)(Br)C(F)(F)Br.Fc1ccc(C23CCCN2CCC3)cn1>C1CCOC1>Fc1ncc(C23CCCN2CCC3)cc1Br
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-a8c5c25f4fb846a89628f7a3b1c115e3
Fc1ncc(C23CCCN2CCC3)cc1Br>>Fc1ncc(C23CCCN2CCC3)cc1Br
Cl.BrC=1C=C(C=NC1F)C12CCCN2CCC1>>Cl.BrC=1C=C(C=NC1F)C12CCCN2CCC1
[F:2][c:3]1[n:4][cH:5][c:6]([C:7]23[CH2:8][CH2:9][CH2:10][N:11]2[CH2:12][CH2:13][CH2:14]3)[cH:15][c:16]1[Br:17]>>[F:2][c:3]1[n:4][cH:5][c:6]([C:7]23[CH2:8][CH2:9][CH2:10][N:11]2[CH2:12][CH2:13][CH2:14]3)[cH:15][c:16]1[Br:17]
Fc1ncc(C23CCCN2CCC3)cc1Br
Fc1ncc(C23CCCN2CCC3)cc1Br
null
null
CCOCC
Miscellaneous
OtherReaction
40ba59785861b8226ce5af6bdcbb9a37f0ff50a8c7ec7d4fc4c524cf906cc65c
56ebed4a8b3cebec83c37a71d68f0c87d1e404ab05a9ce792691e4e18a2379dd
c1cncc(C23CCCN2CCC3)c1
null
87
[{"value": 87.0, "product": "Cl.BrC=1C=C(C=NC1F)C12CCCN2CCC1", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
7a-(5-bromo-6-fluoro-3-pyridinyl)-hexahydro-1H-pyrrolizine was dissolved in Et2O, and Et2O saturated with HCl (g) was added. The solvent was removed, and the solid was triturated with Et2O and dried to afford the title compound as a white powder (59 mg, 87%): mp 213°-215° C.; 1H NMR D2O, 300 MHz) δ2.15-2.49 (m, 6H), 2....
10.6084/m9.figshare.5104873.v1
null
null
null
null
null
c1ccncc1.C1CC2CCCN2C1
null
CCOCC
null
null
Fc1ncc(C23CCCN2CCC3)cc1Br>CCOCC>Fc1ncc(C23CCCN2CCC3)cc1Br
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-00bd9856a1bd4532834dd176039f25ee
ClC(Cl)(Cl)C(Cl)(Cl)Cl.Fc1ccc(C23CCCN2CCC3)cn1>>Fc1ncc(C23CCCN2CCC3)cc1Cl
[Li]CCCC.C(C)(C)NC(C)C.FC1=CC=C(C=N1)C12CCCN2CCC1.ClC(C(Cl)(Cl)Cl)(Cl)Cl>>ClC=1C=C(C=NC1F)C12CCCN2CCC1
ClC(Cl)(Cl)C(Cl)(Cl)[Cl:16].[F:1][c:2]1[n:3][cH:4][c:5]([C:6]23[CH2:7][CH2:8][CH2:9][N:10]2[CH2:11][CH2:12][CH2:13]3)[cH:14][cH:15]1>>[F:1][c:2]1[n:3][cH:4][c:5]([C:6]23[CH2:7][CH2:8][CH2:9][N:10]2[CH2:11][CH2:12][CH2:13]3)[cH:14][c:15]1[Cl:16]
ClC(Cl)(Cl)C(Cl)(Cl)Cl.Fc1ccc(C23CCCN2CCC3)cn1
Fc1ncc(C23CCCN2CCC3)cc1Cl
null
null
C1CCOC1
Functional Group Interconversion
Chlorination
b6bfd9375f1a0668183fe0de435085183ec91305a2e1dcb5397f52bc008dc1b3
5299dd3c496bc7c94739e7d10382eb68ebc90d6d6c0c125f886657d3b41caf21
c1cncc(C23CCCN2CCC3)c1
Cl-C(-Cl)(-Cl)-C(-Cl)(-Cl)-[Cl;H0;D1;+0:1].[F;D1;H0:2]-[c:3]1:[#7;a:4]:[c:5]:[c:6]:[c:7]:[cH;D2;+0:8]:1>>[Cl;H0;D1;+0:1]-[c;H0;D3;+0:8]1:[c:7]:[c:6]:[c:5]:[#7;a:4]:[c:3]:1-[F;D1;H0:2]
34
[{"value": 34.0, "product": "ClC=1C=C(C=NC1F)C12CCCN2CCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 33.4, "product": "ClC=1C=C(C=NC1F)C12CCCN2CCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
15
MINUTE
n-BuLi (2.5M in hexanes, 0.232 mL, 0.58 mmol) was added to di-isopropylamine (0.077 mL, 0.58 mmol) in THF and stirred at room temperature for 15 minutes, then cooled to -78° C. 7a-(6-Fluoro-3-pyridinyl)-hexahydro-1H-pyrrolizine (115 mg, 0.56 mmol, from Example 12d) and hexachloroethane (400 mg, 1.7 mmol) were added. Th...
10.6084/m9.figshare.5104873.v1
null
Trichloro group.Trichloro group
Aromatic halide
c1ccncc1
c1ccncc1
c1ccncc1.C1CC2CCCN2C1
HCl
C1CCOC1
null
0.25
ClC(Cl)(Cl)C(Cl)(Cl)Cl.Fc1ccc(C23CCCN2CCC3)cn1>C1CCOC1>Fc1ncc(C23CCCN2CCC3)cc1Cl
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-de9abf64e74b42648268c346ed5db6f3
Fc1ncc(C23CCCN2CCC3)cc1Cl>>Fc1ncc(C23CCCN2CCC3)cc1Cl
Cl.ClC=1C=C(C=NC1F)C12CCCN2CCC1>>Cl.ClC=1C=C(C=NC1F)C12CCCN2CCC1
[F:2][c:3]1[n:4][cH:5][c:6]([C:7]23[CH2:8][CH2:9][CH2:10][N:11]2[CH2:12][CH2:13][CH2:14]3)[cH:15][c:16]1[Cl:17]>>[F:2][c:3]1[n:4][cH:5][c:6]([C:7]23[CH2:8][CH2:9][CH2:10][N:11]2[CH2:12][CH2:13][CH2:14]3)[cH:15][c:16]1[Cl:17]
Fc1ncc(C23CCCN2CCC3)cc1Cl
Fc1ncc(C23CCCN2CCC3)cc1Cl
null
null
CCOCC
Miscellaneous
OtherReaction
40ba59785861b8226ce5af6bdcbb9a37f0ff50a8c7ec7d4fc4c524cf906cc65c
56ebed4a8b3cebec83c37a71d68f0c87d1e404ab05a9ce792691e4e18a2379dd
c1cncc(C23CCCN2CCC3)c1
null
74
[{"value": 74.0, "product": "Cl.ClC=1C=C(C=NC1F)C12CCCN2CCC1", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
7a-(5-chloro-6-fluoro-3-pyridinyl)-hexahydro-1H-pyrrolizine was dissolved in Et2O, and Et2O saturated with HCl (g) was added. The solvent was removed, and the solid was triturated with Et2O and dried to afford the title compound as a white powder (35 mg, 74%): mp 181°-183° C.; 1H NMR (D2O, 300 MHz) δ2.15-2.50 (m, 6H), ...
10.6084/m9.figshare.5104873.v1
null
null
null
null
null
c1ccncc1.C1CC2CCCN2C1
null
CCOCC
null
null
Fc1ncc(C23CCCN2CCC3)cc1Cl>CCOCC>Fc1ncc(C23CCCN2CCC3)cc1Cl
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-25cc9381e06f48dab75a6ffa0b61c21d
C1CC2=[N+](C1)CCC2.Cc1ccncc1I>>Cc1ccncc1C12CCCN1CCC2
IC=1C=NC=CC1C.[Li]C(C)(C)C.Cl(=O)(=O)(=O)[O-].C1CC[N+]=2CCCC12>>CC1=C(C=NC=C1)C12CCCN2CCC1
[C:8]12=[N+:12]([CH2:11][CH2:10][CH2:9]1)[CH2:13][CH2:14][CH2:15]2.I[c:7]1[c:2]([CH3:1])[cH:3][cH:4][n:5][cH:6]1>>[CH3:1][c:2]1[cH:3][cH:4][n:5][cH:6][c:7]1[C:8]12[CH2:9][CH2:10][CH2:11][N:12]1[CH2:13][CH2:14][CH2:15]2
C1CC2=[N+](C1)CCC2.Cc1ccncc1I
Cc1ccncc1C12CCCN1CCC2
null
null
CCCCC.CCOCC
Functional Group Interconversion
OtherReaction
6e757ff9396a07e923211312afac1c080dd23eff3444ff9c846ed5fe9d4243b6
773dbb8365a8bceadef31887b9f43d5f4f5443038ea5ede92ac6bcd66c5d17b4
c1cncc(C23CCCN2CCC3)c1
I-[c;H0;D3;+0:1]1:[c:2]:[#7;a:3]:[c:4]:[c:5]:[c:6]:1-[C;D1;H3:7].[C:8]1-[C:9]-[N+;H0;D3:10]2=[C;H0;D3;+0:11](-[C:12]-[C:13]-[C:14]-2)-[C:15]-1>>[C;D1;H3:7]-[c:6]1:[c:5]:[c:4]:[#7;a:3]:[c:2]:[c;H0;D3;+0:1]:1-[C;H0;D4;+0:11]12-[C:12]-[C:13]-[C:14]-[N;H0;D3;+0:10]-1-[C:9]-[C:8]-[C:15]-2
6.5
[{"value": 6.0, "product": "CC1=C(C=NC=C1)C12CCCN2CCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 6.5, "product": "CC1=C(C=NC=C1)C12CCCN2CCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
-95
CELSIUS
2
HOUR
3-Iodo-4-methylpyridine (330 mg, 3.10 mmol) was dissolved in Et2O and cooled to -95° C. A solution of t-BuLi (1.7M in pentane, 4.0 ml, 6.80 mmol) in pentane was added dropwise. 1,2,3,5,6,7-hexahydropyrrolizinium perchlorate (960 mg, 4.60 mmol) was added, and the reaction mixture was allowed to warm to -10° C. with stir...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
Tertiary amine
C1CC2=[N+](C1)CCC2.c1ccncc1
c1ccncc1.C1CC2CCCN2C1
c1ccncc1.C1CC2CCCN2C1
I-
CCCCC.CCOCC
-95
2
C1CC2=[N+](C1)CCC2.Cc1ccncc1I>CCCCC.CCOCC>Cc1ccncc1C12CCCN1CCC2
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-9f0d302e51834ee5ae59f2e30cfe7ffc
Cl>>Cl.Cl
Cl.CC1=C(C=NC=C1)C12CCCN2CCC1>>Cl.Cl.CC1=C(C=NC=C1)C12CCCN2CCC1
[ClH:16]>>[ClH:16].[ClH:17]
Cl
Cl.Cl
null
null
CCOCC
Miscellaneous
OtherReaction
40ba59785861b8226ce5af6bdcbb9a37f0ff50a8c7ec7d4fc4c524cf906cc65c
56ebed4a8b3cebec83c37a71d68f0c87d1e404ab05a9ce792691e4e18a2379dd
null
null
61
[{"value": 61.0, "product": "Cl.Cl.CC1=C(C=NC=C1)C12CCCN2CCC1", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
7a-(4-methyl-3-pyridinyl)-hexahydro-1H-pyrrolizine (37 mg, 0.18 mmol) was dissolved in Et2O, and Et2O saturated with HCl (g) was added. The solvent was removed, and the solid was triturated with Et2O and dried to afford the title compound as a white solid (26.2 mg, 61%): mp 244°-247° C.; 1H NMR D2O, 300 MHz) δ2.01-2.16...
10.6084/m9.figshare.5104873.v1
null
null
null
null
null
null
Other
CCOCC
null
null
Cl>CCOCC>Cl.Cl
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-f04c2e1d91b841f084faee8cc1432b9f
Brc1cncc(Br)c1.OB(O)c1ccccc1>>Brc1cncc(-c2ccccc2)c1
BrC=1C=NC=C(C1)Br.C1(=CC=CC=C1)B(O)O.C([O-])([O-])=O.[Na+].[Na+]>>BrC=1C=NC=C(C1)C1=CC=CC=C1
Br[c:6]1[cH:5][n:4][cH:3][c:2]([Br:1])[cH:13]1.OB(O)[c:7]1[cH:8][cH:9][cH:10][cH:11][cH:12]1>>[Br:1][c:2]1[cH:3][n:4][cH:5][c:6](-[c:7]2[cH:8][cH:9][cH:10][cH:11][cH:12]2)[cH:13]1
Brc1cncc(Br)c1.OB(O)c1ccccc1
Brc1cncc(-c2ccccc2)c1
null
C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.[Pd]
C1(=CC=CC=C1)C
C-C Coupling
Suzuki coupling with boronic acids
07e9b6e71d806aa92d4573f3838e77c7c8344de3e5d5735ebdb5fc6862ebf27d
08d2969413ef1a2cd5b43667268ba178160c7b55545bf48018e31f2b019632ec
c1ccc(-c2cccnc2)cc1
Br-[c;H0;D3;+0:1]1:[c:2]:[c:3]:[c:4]:[#7;a:5]:[c:6]:1.O-B(-O)-[c;H0;D3;+0:7](:[c:8]:[c:9]):[c:10]:[c:11]>>[c:9]:[c:8]:[c;H0;D3;+0:7](-[c;H0;D3;+0:1]1:[c:2]:[c:3]:[c:4]:[#7;a:5]:[c:6]:1):[c:10]:[c:11]
null
[]
null
null
null
null
Portions of 3,5-dibromopyridine (1.0 g, 4.22 mmol), phenylboronic acid (570 mg, 4.6 mmol) and palladium tetra(triphenylphosphine) (60 mg) were combined in toluene (20 mL) with aqueous sodium carbonate solution (2M, 3.0 mL) and heated at reflux for 6 hours. The mixture was cooled to ambient temperature, and the solvent ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Boronic acid
null
c1ccncc1.c1ccccc1
c1ccncc1.c1ccccc1
c1ccncc1.c1ccccc1
HBr.B
C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.[Pd].C1(=CC=CC=C1)C
null
null
Brc1cncc(Br)c1.OB(O)c1ccccc1>C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.[Pd].C1(=CC=CC=C1)C>Brc1cncc(-c2ccccc2)c1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-5b22770333014a4da72ab520662759f7
BrC1(c2ccccc2)C=CC=NC1.C1CC2=[N+](C1)CCC2>>c1ccc(-c2cncc(C34CCCN3CCC4)c2)cc1
Cl.BrC1(CN=CC=C1)C1=CC=CC=C1.[Li]C(C)(C)C.Cl(=O)(=O)(=O)[O-].C1CC[N+]=2CCCC12>>C1(=CC=CC=C1)C=1C=C(C=NC1)C12CCCN2CCC1
Br[C:5]1([c:4]2[cH:3][cH:2][cH:1][cH:20][cH:19]2)[CH2:6][N:7]=[CH:8][CH:9]=[CH:18]1.[C:10]12=[N+:14]([CH2:13][CH2:12][CH2:11]1)[CH2:15][CH2:16][CH2:17]2>>[cH:1]1[cH:2][cH:3][c:4](-[c:5]2[cH:6][n:7][cH:8][c:9]([C:10]34[CH2:11][CH2:12][CH2:13][N:14]3[CH2:15][CH2:16][CH2:17]4)[cH:18]2)[cH:19][cH:20]1
BrC1(c2ccccc2)C=CC=NC1.C1CC2=[N+](C1)CCC2
c1ccc(-c2cncc(C34CCCN3CCC4)c2)cc1
null
null
CCCCC.CCOCC
Aromatic Heterocycle Formation
OtherReaction
a2ceb260427fba4f3cceb32f0ad8f9216c0c2ec29532e72b1ad28507408fe0c8
ec642e2a2ffda901ebc676763ee3ceea45718d26f8ee90442c60d1ad2244e11f
c1ccc(-c2cncc(C34CCCN3CCC4)c2)cc1
Br-[C;H0;D4;+0:1]1(-[c;H0;D3;+0:2](:[c:3]:[c:4]):[c:5]:[c:6])-[CH2;D2;+0:7]-[N;H0;D2;+0:8]=[CH;D2;+0:9]-[CH;D2;+0:10]=[CH;D2;+0:11]-1.[C:12]1-[C:13]-[C:14]-[N+;H0;D3:15]2=[C;H0;D3;+0:16]-1-[C:17]-[C:18]-[C:19]-2>>[c:4]:[c:3]:[c;H0;D3;+0:2](-[c;H0;D3;+0:1]1:[cH;D2;+0:11]:[c;H0;D3;+0:10](-[C;H0;D4;+0:16]23-[C:12]-[C:13]-...
14.5
[{"value": 14.5, "product": "C1(=CC=CC=C1)C=1C=C(C=NC1)C12CCCN2CCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
-30
CELSIUS
10
MINUTE
3-Bromo-3-phenylpyridine (200 mg, 0.85 mmol) was dissolved in Et2O and cooled to -30° C. A solution of 2.5M t-BuLi (1.1 mL, 1.90 mmol) in pentane was added, and the reaction was stirred for 10 minutes. 1,2,3,5,6,7-Hexahydropyrrolizinium perchlorate (230 mg, 1.30 mmol) was added, and the reaction mixture was allowed to ...
10.6084/m9.figshare.5104873.v1
null
Tertiary halide.Substituted imine
Tertiary amine
C1=CCCN=C1.C1CC2=[N+](C1)CCC2
c1ccncc1.C1CC2CCCN2C1
c1ccccc1.c1ccncc1.C1CC2CCCN2C1
HBr
CCCCC.CCOCC
-30
0.166667
BrC1(c2ccccc2)C=CC=NC1.C1CC2=[N+](C1)CCC2>CCCCC.CCOCC>c1ccc(-c2cncc(C34CCCN3CCC4)c2)cc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-67e631af3ef64f0490cab77fef17bd5e
c1ccc(-c2cncc(C34CCCN3CCC4)c2)cc1>>c1ccc(-c2cncc(C34CCCN3CCC4)c2)cc1
Cl.C1(=CC=CC=C1)C=1C=C(C=NC1)C12CCCN2CCC1>>Cl.C1(=CC=CC=C1)C=1C=C(C=NC1)C12CCCN2CCC1
[cH:2]1[cH:3][cH:4][c:5](-[c:6]2[cH:7][n:8][cH:9][c:10]([C:11]34[CH2:12][CH2:13][CH2:14][N:15]3[CH2:16][CH2:17][CH2:18]4)[cH:19]2)[cH:20][cH:21]1>>[cH:2]1[cH:3][cH:4][c:5](-[c:6]2[cH:7][n:8][cH:9][c:10]([C:11]34[CH2:12][CH2:13][CH2:14][N:15]3[CH2:16][CH2:17][CH2:18]4)[cH:19]2)[cH:20][cH:21]1
c1ccc(-c2cncc(C34CCCN3CCC4)c2)cc1
c1ccc(-c2cncc(C34CCCN3CCC4)c2)cc1
null
null
CCOCC
Miscellaneous
OtherReaction
40ba59785861b8226ce5af6bdcbb9a37f0ff50a8c7ec7d4fc4c524cf906cc65c
56ebed4a8b3cebec83c37a71d68f0c87d1e404ab05a9ce792691e4e18a2379dd
c1ccc(-c2cncc(C34CCCN3CCC4)c2)cc1
null
null
[]
null
null
null
null
The 7a-(5-phenyl-3-pyridinyl)-hexahydro-1H-pyrrolizine compound from step 25b was dissolved in ether (5 mL) and Et2O saturated with HCl (g) was added. The solvent was removed, and the solid was dried to afford the title compound as yellow needles (13.5 mg): mp 217°-220° C. (dec.); 1H NMR D2O, 300 MHz) δ2.17-2.47 (m, 4H...
10.6084/m9.figshare.5104873.v1
null
null
null
null
null
c1ccccc1.c1ccncc1.C1CC2CCCN2C1
null
CCOCC
null
null
c1ccc(-c2cncc(C34CCCN3CCC4)c2)cc1>CCOCC>c1ccc(-c2cncc(C34CCCN3CCC4)c2)cc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-59a65a7056d742c49de82eb5c63762a4
CC(C)(C)OC(=O)N=C(NCCCCCCNC(=O)CN)NC(=O)OC(C)(C)C.CC(C)(C)OC(=O)NCCCN(CCCCO)C(=O)OC(C)(C)C.O=C(Cl)Oc1ccc([N+](=O)[O-])cc1>>CC(C)(C)OC(=O)N=C(NCCCCCCNC(=O)CNC(=O)OCCCCN(CCCNC(=O)OC(C)(C)C)C(=O)OC(C)(C)C)NC(=O)OC(C)(C)C
ClC(=O)OC1=CC=C(C=C1)[N+](=O)[O-].NCC(NCCCCCCNC(=NC(=O)OC(C)(C)C)NC(=O)OC(C)(C)C)=O.CC(C)(OC(=O)NCCCN(C(OC(C)(C)C)=O)CCCCO)C.C(C)N(CC)CC>>CC(C)(OC(=O)NC(=NC(=O)OC(C)(C)C)NCCCCCCNC(CNC(OCCCCN(CCCNC(=O)OC(C)(C)C)C(=O)OC(C)(C)C)=O)=O)C
[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]=[C:9]([NH:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][NH:17][C:18](=[O:19])[CH2:20][NH2:21])[NH:48][C:49](=[O:50])[O:51][C:52]([CH3:53])([CH3:54])[CH3:55].[OH:24][CH2:25][CH2:26][CH2:27][CH2:28][N:29]([CH2:30][CH2:31][CH2:32][NH:33][C:34](=[O:35])[O:36][C:37...
CC(C)(C)OC(=O)N=C(NCCCCCCNC(=O)CN)NC(=O)OC(C)(C)C.CC(C)(C)OC(=O)NCCCN(CCCCO)C(=O)OC(C)(C)C.O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
CC(C)(C)OC(=O)N=C(NCCCCCCNC(=O)CNC(=O)OCCCCN(CCCNC(=O)OC(C)(C)C)C(=O)OC(C)(C)C)NC(=O)OC(C)(C)C
null
null
C(C)(=O)OCC.O1CCCC1
Functional Group Interconversion
OtherReaction
efbcb474775e37b1c3f28b3cc99478861fbf52e5dd627e50d041f406eb58eb1c
f145f943676713212a06a6fc1485be73591da940d9f647b06c145d0e822eca44
null
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-O-c1:c:c:c(-[N+](=O)-[O-]):c:c:1.[C:3]-[#7:4]-[C:5](=[O;D1;H0:6])-[C:7]-[NH2;D1;+0:8].[C:9]-[C:10]-[OH;D1;+0:11]>>[C:3]-[#7:4]-[C:5](=[O;D1;H0:6])-[C:7]-[NH;D2;+0:8]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[O;H0;D2;+0:11]-[C:10]-[C:9]
44
[{"value": 44.0, "product": null, "details": "PERCENTYIELD", "is_desired": false}]
null
null
15
HOUR
1 g (2.89·10-3 mol) of [3-[[(1,1-dimethyl-ethoxy)carbonyl]amino]propyl](4-hydroxybutyl)carbamic acid, 1,1-dimethylethyl ester is dissolved in 20 ml of tetrahydrofuran (THF), and 0.45 g (4.5·10-3 mol) of triethylamine is added followed by a solution of 0.58 g (2.89·10-3 mol) of 4-nitrophenyl chloroformate in 5 ml of THF...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Ether.Nitro group.Primary alcohol.Primary amine
Carbamic ester
c1ccccc1
null
null
HCl
C(C)(=O)OCC.O1CCCC1
null
15
CC(C)(C)OC(=O)N=C(NCCCCCCNC(=O)CN)NC(=O)OC(C)(C)C.CC(C)(C)OC(=O)NCCCN(CCCCO)C(=O)OC(C)(C)C.O=C(Cl)Oc1ccc([N+](=O)[O-])cc1>C(C)(=O)OCC.O1CCCC1>CC(C)(C)OC(=O)N=C(NCCCCCCNC(=O)CNC(=O)OCCCCN(CCCNC(=O)OC(C)(C)C)C(=O)OC(C)(C)C)NC(=O)OC(C)(C)C
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-f0e0f1638dcd40c780aa7d8ec6375945
CCOC(=O)CNC(=O)CCCCCBr.[C-]#N>>CCOC(=O)CNC(=O)CCCCCC#N
BrCCCCCC(=O)NCC(=O)OCC.[C-]#N.[K+].ClCCl>>C(#N)CCCCCC(=O)NCC(=O)OCC
Br[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][C:8]([NH:7][CH2:6][C:4]([O:3][CH2:2][CH3:1])=[O:5])=[O:9].[C-:15]#[N:16]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH2:6][NH:7][C:8](=[O:9])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]#[N:16]
CCOC(=O)CNC(=O)CCCCCBr.[C-]#N
CCOC(=O)CNC(=O)CCCCCC#N
null
null
C(C)O
C-C Coupling
OtherReaction
347b040e695b34bb71d78d55beea9c7162795a061d052426f1f803b52c4cbe4d
1dbefa1fc17e03074aa3f6619987f71dfa9a1cb0d61de142a880cd3f05e4f004
null
Br-[CH2;D2;+0:1]-[C:2]-[C:3].[C-;H0;D1:4]#[N;D1;H0:5]>>[C:3]-[C:2]-[CH2;D2;+0:1]-[C;H0;D2;+0:4]#[N;D1;H0:5]
99
[{"value": 99.0, "product": "C(#N)CCCCCC(=O)NCC(=O)OCC", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
23.73 g (84.7·10-3 mol) of N-(6-bromohexanoyl)-glycine, ethyl ester are dissolved in 200 ml of ethanol, and 6.5 g (0.1 mol) of powdered potassium cyanide are added. The reaction mixture is brought to the reflux point and stirred under reflux for 15 hours. After concentration of the mixture under reduced pressure, the r...
10.6084/m9.figshare.5104873.v1
null
Primary halide
Nitrile
null
null
null
Br-
C(C)O
null
null
CCOC(=O)CNC(=O)CCCCCBr.[C-]#N>C(C)O>CCOC(=O)CNC(=O)CCCCCC#N
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-ae97e9d0be094c7d859d65239405a8ff
N#CCCCCCC(=O)NCC(=O)O>>NCCCCCCC(=O)NCC(=O)O
[OH-].[Na+].C(#N)CCCCCC(=O)NCC(=O)O.[Cl-].[Na+].Cl>>NCCCCCCC(=O)NCC(=O)O
[N:1]#[C:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][C:8](=[O:9])[NH:10][CH2:11][C:12](=[O:13])[OH:14]>>[NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][C:8](=[O:9])[NH:10][CH2:11][C:12](=[O:13])[OH:14]
N#CCCCCCC(=O)NCC(=O)O
NCCCCCCC(=O)NCC(=O)O
null
[Ni]
C(C)O
Reduction
Reduction of nitrile to amine
65bec2d9f430701d30dc9fcbe1c5418f3dfa174d67be035c50edfc71895dc9c7
e8d1bc928b94bd4f5bf4b23363ce8f88b1ce7d146ba93829e7b8ad8dbe0007a7
null
[C:1]-[C:2]-[C;H0;D2;+0:3]#[N;H0;D1;+0:4]>>[C:1]-[C:2]-[CH2;D2;+0:3]-[NH2;D1;+0:4]
null
[]
null
null
8
HOUR
8.2 g (41.4·10-3 mol) of N-(6-cyanohexanoyl)-glycine are dissolved in 100 ml of ethanol, and 60 ml of 1M sodium hydroxide solution and 800 mg of Raney nickel are added. The mixture is then stirred under a hydrogen atmosphere, at room temperature and under a pressure of 3.5·105Pa, for 8 hours. When the reaction has ende...
10.6084/m9.figshare.5104873.v1
null
Nitrile
Primary amine
null
null
null
null
[Ni].C(C)O
null
8
N#CCCCCCC(=O)NCC(=O)O>[Ni].C(C)O>NCCCCCCC(=O)NCC(=O)O
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-8c72bfcb26eb4ce38bf4d9fcc1fda530
BrCc1ccccc1.COc1cccc2[nH]c(C)cc12>>COc1cccc2c1cc(C)n2Cc1ccccc1
C(C1=CC=CC=C1)Br.COC1=C2C=C(NC2=CC=C1)C.[H-].[Na+].CCCCCC>>COC1=C2C=C(N(C2=CC=C1)CC1=CC=CC=C1)C
Br[CH2:13][c:14]1[cH:15][cH:16][cH:17][cH:18][cH:19]1.[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][c:7]2[c:8]1[cH:9][c:10]([CH3:11])[nH:12]2>>[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][c:7]2[c:8]1[cH:9][c:10]([CH3:11])[n:12]2[CH2:13][c:14]1[cH:15][cH:16][cH:17][cH:18][cH:19]1
BrCc1ccccc1.COc1cccc2[nH]c(C)cc12
COc1cccc2c1cc(C)n2Cc1ccccc1
null
null
CN(C)C=O.O
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
16b46a8af20339f7ff0b611b4ac5dd01fe35ba577361e893c359dfa478dc1974
2e1e5fd9557b69cb528f6b2ffd179c67ef24ecb1a2c3994e1cdf0efe7ae19e9c
c1ccc(Cn2ccc3ccccc32)cc1
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[C;D1;H3:5]-[c:6]1:[c:7]:[c:8]:[c:9](:[c:10]):[nH;D2;+0:11]:1>>[C;D1;H3:5]-[c:6]1:[c:7]:[c:8]:[c:9](:[c:10]):[n;H0;D3;+0:11]:1-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4]
84
[{"value": 84.0, "product": "COC1=C2C=C(N(C2=CC=C1)CC1=CC=CC=C1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 83.4, "product": "COC1=C2C=C(N(C2=CC=C1)CC1=CC=CC=C1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
0.5
HOUR
4-Methoxy-2-methyl-1H-indole (1 g, 6.2 mmol) was added to 248 mg (6.2 mmol) of 60% sodium hydride/mineral oil (washed with hexane before adding DMF) in 15 mL of DMF and after stirring for 0.5 hour, 0.74 mL (6.2 mmol) of benzyl bromide was added. The mixture was stirred at room temperature for 18 hours, diluted with wat...
10.6084/m9.figshare.5104873.v1
null
Primary halide
null
c1ccc2[nH]ccc2c1
c1cc2ccccc2[nH]1
c1cc2ccccc2[nH]1.c1ccccc1
HBr
CN(C)C=O.O
null
0.5
BrCc1ccccc1.COc1cccc2[nH]c(C)cc12>CN(C)C=O.O>COc1cccc2c1cc(C)n2Cc1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-b929091e25a74504966cd0bf54a67e49
COc1cccc2c1cc(C)n2Cc1ccccc1>>Cc1cc2c(O)cccc2n1Cc1ccccc1
COC1=C2C=C(N(C2=CC=C1)CC1=CC=CC=C1)C.B(Br)(Br)Br.C(Cl)Cl>>OC1=C2C=C(N(C2=CC=C1)CC1=CC=CC=C1)C
C[O:6][c:5]1[c:4]2[cH:3][c:2]([CH3:1])[n:11]([CH2:12][c:13]3[cH:14][cH:15][cH:16][cH:17][cH:18]3)[c:10]2[cH:9][cH:8][cH:7]1>>[CH3:1][c:2]1[cH:3][c:4]2[c:5]([OH:6])[cH:7][cH:8][cH:9][c:10]2[n:11]1[CH2:12][c:13]1[cH:14][cH:15][cH:16][cH:17][cH:18]1
COc1cccc2c1cc(C)n2Cc1ccccc1
Cc1cc2c(O)cccc2n1Cc1ccccc1
null
null
C(Cl)Cl
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc(Cn2ccc3ccccc32)cc1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]:[c:5]:[#7;a:6]>>[#7;a:6]:[c:5]:[c:4]:[c:2](-[OH;D1;+0:1]):[c:3]
49
[{"value": 49.0, "product": "OC1=C2C=C(N(C2=CC=C1)CC1=CC=CC=C1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 48.6, "product": "OC1=C2C=C(N(C2=CC=C1)CC1=CC=CC=C1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 1.25 g (5 mmol) of 4-methoxy-2-methyl-1-(phenylmethyl)-1H-indole and 20 mL of 1M BBr3 /CH2Cl2 in 50 mL of methylene chloride was stirred at room temperature for 5 hours and concentrated at reduced pressure. The residue was dissolved in ethyl acetate, washed with brine and dried (MgSO4). After concentratin...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1cc2ccccc2[nH]1.c1ccccc1
Other
C(Cl)Cl
null
null
COc1cccc2c1cc(C)n2Cc1ccccc1>C(Cl)Cl>Cc1cc2c(O)cccc2n1Cc1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-19b0abee38be4025b9f496f094d7d0bd
COC(=O)CBr.Cc1cc2c(O)cccc2n1Cc1ccccc1>>COC(=O)COc1cccc2c1cc(C)n2Cc1ccccc1
OC1=C2C=C(N(C2=CC=C1)CC1=CC=CC=C1)C.[H-].[Na+].BrCC(=O)OC>>COC(COC1=C2C=C(N(C2=CC=C1)CC1=CC=CC=C1)C)=O
Br[CH2:5][C:3]([O:2][CH3:1])=[O:4].[OH:6][c:7]1[cH:8][cH:9][cH:10][c:11]2[c:12]1[cH:13][c:14]([CH3:15])[n:16]2[CH2:17][c:18]1[cH:19][cH:20][cH:21][cH:22][cH:23]1>>[CH3:1][O:2][C:3](=[O:4])[CH2:5][O:6][c:7]1[cH:8][cH:9][cH:10][c:11]2[c:12]1[cH:13][c:14]([CH3:15])[n:16]2[CH2:17][c:18]1[cH:19][cH:20][cH:21][cH:22][cH:23]1
COC(=O)CBr.Cc1cc2c(O)cccc2n1Cc1ccccc1
COC(=O)COc1cccc2c1cc(C)n2Cc1ccccc1
null
null
CN(C)C=O.O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
50d675b335c583a6ce22e1164b27a78b18b9ca447d45137820c344bcb6369217
0865de4e1853c59ac25437e36fd18b03329566cb9eff4b4f0ce70d5714692fd3
c1ccc(Cn2ccc3ccccc32)cc1
Br-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5].[#7;a:6]:[c:7]:[c:8]:[c:9](-[OH;D1;+0:10]):[c:11]>>[#7;a:6]:[c:7]:[c:8]:[c:9](-[O;H0;D2;+0:10]-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5]):[c:11]
88
[{"value": 88.0, "product": "COC(COC1=C2C=C(N(C2=CC=C1)CC1=CC=CC=C1)C)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 87.7, "product": "COC(COC1=C2C=C(N(C2=CC=C1)CC1=CC=CC=C1)C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
0.67
HOUR
4-Hydroxy-2-methyl-1-(phenylmethyl)-1H-indole (530 mg, 2.2 mmol) was added to 88 mg (2.2 mmol) of 60% NaH/mineral oil in 20 mL of DMF and the mixture stirred for 0.67 hours. Then, 0.21 mL (2.2 mmol) of methyl bromoacetate was added and stirring maintained for 17 hours. The mixture was diluted with water and extracted w...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester.Aromatic alcohol
Ester.Ether
null
null
c1cc2ccccc2[nH]1.c1ccccc1
HBr
CN(C)C=O.O
null
0.67
COC(=O)CBr.Cc1cc2c(O)cccc2n1Cc1ccccc1>CN(C)C=O.O>COC(=O)COc1cccc2c1cc(C)n2Cc1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-1c51dd5042944cafbcc75002bd31f9d1
COC(=O)C(C)Br.Cc1cc2c(O)cccc2n1Cc1ccccc1>>CCCCCC.CCOC(C)=O.COC(=O)C(C)Oc1cccc2c1cc(C)n2Cc1ccccc1
OC1=C2C=C(N(C2=CC=C1)CC1=CC=CC=C1)C.[H-].[Na+].BrC(C(=O)OC)C>>COC(C(C)OC1=C2C=C(N(C2=CC=C1)CC1=CC=CC=C1)C)=O.CCOC(=O)C.CCCCCC
Br[CH:17]([C:15](=[O:9])[O:14][CH3:13])[CH3:18].[cH:1]1[cH:32][c:31]([CH2:30][n:29]2[c:24]3[cH:23][cH:22][cH:21][c:20]([OH:19])[c:25]3[cH:26][c:27]2[CH3:28])[cH:36][cH:35][cH:34]1>>[CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[CH3:7][CH2:8][O:9][C:10]([CH3:11])=[O:12].[CH3:13][O:14][C:15](=[O:16])[CH:17]([CH3:18])[O:19][...
COC(=O)C(C)Br.Cc1cc2c(O)cccc2n1Cc1ccccc1
CCCCCC.CCOC(C)=O.COC(=O)C(C)Oc1cccc2c1cc(C)n2Cc1ccccc1
null
null
CN(C)C=O
Acylation
Williamson Ether Synthesis
c05decc99b0034b12abc4520661d3e2054665934b67ff4efc33902f234192ca4
8e21a061e9e5b3d6a55f77e57128b08e82eb226539ffc927f65ff0ec9c28e997
c1ccc(Cn2ccc3ccccc32)cc1
Br-[CH;D3;+0:1](-[C;D1;H3:2])-[C;H0;D3;+0:3](=[O;H0;D1;+0:4])-[#8:5]-[C;D1;H3:6].[OH;D1;+0:7]-[c:8](:[c:9]):[c:10]:[c:11]:[#7;a:12]-[C:13]-[c:14]1:[c:15]:[c:16]:[cH;D2;+0:17]:[cH;D2;+0:18]:[cH;D2;+0:19]:1>>[C;D1;H3:6]-[#8:5]-[C;H0;D3;+0:3](=[O;D1;H0:20])-[CH;D3;+0:1](-[C;D1;H3:2])-[O;H0;D2;+0:7]-[c:8](:[c:9]):[c:10]:[c...
74
[{"value": 74.0, "product": "CCOC(=O)C.CCCCCC", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
4-Hydroxy-2-methyl-1-(phenylmethyl)-1H-indole (483 mg, 2.0 mmol) was reacted with 82 mg (2.0 mmol) of 60% NaH/mineral oil in 20 mL of DMF and then with 0.22 mL (2.0 mmol) of dl-methyl 2-bromopropionate as described in Example 1, Part E to give after chromatography on silica gel eluting with 20% EtOAc/hexane 480 mg (74%...
10.6084/m9.figshare.5104873.v1
null
Secondary halide.Ester.Aromatic alcohol
Ester.Ester.Ether
c1ccccc1
c1ccccc1
c1cc2ccccc2[nH]1.c1ccccc1
Br-
CN(C)C=O
null
null
COC(=O)C(C)Br.Cc1cc2c(O)cccc2n1Cc1ccccc1>CN(C)C=O>CCCCCC.CCOC(C)=O.COC(=O)C(C)Oc1cccc2c1cc(C)n2Cc1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-9f95807db7ef46aaa34d1a46e928917e
COC(=O)C(C)Oc1cccc2c1cc(C)n2Cc1ccccc1.N.O=C(Cl)C(=O)Cl>>COC(=O)C(C)Oc1cccc2c1c(C(=O)C(N)=O)c(C)n2Cc1ccccc1
C(C(=O)Cl)(=O)Cl.COC(C(C)OC1=C2C=C(N(C2=CC=C1)CC1=CC=CC=C1)C)=O.N>>NC(C(=O)C1=C(N(C2=CC=CC(=C12)OC(C(=O)OC)C)CC1=CC=CC=C1)C)=O
[CH3:1][O:2][C:3](=[O:4])[CH:5]([CH3:6])[O:7][c:8]1[cH:9][cH:10][cH:11][c:12]2[c:13]1[cH:14][c:20]([CH3:21])[n:22]2[CH2:23][c:24]1[cH:25][cH:26][cH:27][cH:28][cH:29]1.[NH3:18].Cl[C:15](=[O:16])[C:17](Cl)=[O:19]>>[CH3:1][O:2][C:3](=[O:4])[CH:5]([CH3:6])[O:7][c:8]1[cH:9][cH:10][cH:11][c:12]2[c:13]1[c:14]([C:15](=[O:16])[...
COC(=O)C(C)Oc1cccc2c1cc(C)n2Cc1ccccc1.N.O=C(Cl)C(=O)Cl
COC(=O)C(C)Oc1cccc2c1c(C(=O)C(N)=O)c(C)n2Cc1ccccc1
null
null
CCOC(=O)C
Acylation
OtherReaction
2b4e5990a6b486febb67d1205a7fe80512d475c2d7f2428255890f94f2b89b0b
1715a619707b7a78b1352b9fcc0d5da2f43c62973c7a9ceb4f5a9bcbea1c7854
c1ccc(Cn2ccc3ccccc32)cc1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C;H0;D3;+0:3](-Cl)=[O;D1;H0:4].[C:5]-[#7;a:6]1:[c:7](:[c:8]):[c:9](:[c:10]):[cH;D2;+0:11]:[c:12]:1-[C;D1;H3:13].[NH3;D0;+0:14]>>[C:5]-[#7;a:6]1:[c:7](:[c:8]):[c:9](:[c:10]):[c;H0;D3;+0:11](-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C;H0;D3;+0:3](-[NH2;D1;+0:14])=[O;D1;H0:4]):[c:12]:1-[C;D1;H3:13]
90
[{"value": 90.0, "product": "NC(C(=O)C1=C(N(C2=CC=CC(=C12)OC(C(=O)OC)C)CC1=CC=CC=C1)C)=O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Oxalyl chloride (0.16 mL, 1.9 mmol) was reacted with 480 mg (1.5 mmol) of dl-2-[[2-methyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]propanoic acid methyl ester and then reacted with anhydrous ammonia as in Example 1, Part F and the reaction product was dissolved in EtOAc, washed with water, dried (MgSO4) and concentrated. The...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Acyl halide
Ketone.Primary amide
c1cc2ccccc2[nH]1
c1cc2ccccc2[nH]1
c1cc2ccccc2[nH]1.c1ccccc1
HCl
CCOC(=O)C
null
null
COC(=O)C(C)Oc1cccc2c1cc(C)n2Cc1ccccc1.N.O=C(Cl)C(=O)Cl>CCOC(=O)C>COC(=O)C(C)Oc1cccc2c1c(C(=O)C(N)=O)c(C)n2Cc1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-238c88d38f694e3fa5d1ff478152a137
COC(=O)C(C)Oc1cccc2c1c(C(=O)C(N)=O)c(C)n2Cc1ccccc1>>Cc1c(C(=O)C(N)=O)c2c(OC(C)C(=O)O)cccc2n1Cc1ccccc1
COC(C(C)OC1=C2C(=C(N(C2=CC=C1)CC1=CC=CC=C1)C)C(C(=O)N)=O)=O.[OH-].[Na+]>>NC(C(=O)C1=C(N(C2=CC=CC(=C12)OC(C(=O)O)C)CC1=CC=CC=C1)C)=O
C[O:16][C:14]([CH:12]([O:11][c:10]1[c:9]2[c:3]([C:4](=[O:5])[C:6]([NH2:7])=[O:8])[c:2]([CH3:1])[n:21]([CH2:22][c:23]3[cH:24][cH:25][cH:26][cH:27][cH:28]3)[c:20]2[cH:19][cH:18][cH:17]1)[CH3:13])=[O:15]>>[CH3:1][c:2]1[c:3]([C:4](=[O:5])[C:6]([NH2:7])=[O:8])[c:9]2[c:10]([O:11][CH:12]([CH3:13])[C:14](=[O:15])[OH:16])[cH:17...
COC(=O)C(C)Oc1cccc2c1c(C(=O)C(N)=O)c(C)n2Cc1ccccc1
Cc1c(C(=O)C(N)=O)c2c(OC(C)C(=O)O)cccc2n1Cc1ccccc1
null
null
CO
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1ccc(Cn2ccc3ccccc32)cc1
C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
50
[{"value": 50.0, "product": "NC(C(=O)C1=C(N(C2=CC=CC(=C12)OC(C(=O)O)C)CC1=CC=CC=C1)C)=O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
0.5
HOUR
A mixture of 521 mg (1.3 mmol) of dl-2-[[3-(2-amino-1,2-dioxoethyl)-2-methyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]propanoic acid methyl ester and 10 mL of 1N NaOH in 30 mL of methanol was heated to maintain reflux for 0.17 hours, cooled to room temperature and stirred for 0.5 hour. The mixture was concentrated at reduced...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1cc2ccccc2[nH]1.c1ccccc1
Other
CO
null
0.5
COC(=O)C(C)Oc1cccc2c1c(C(=O)C(N)=O)c(C)n2Cc1ccccc1>CO>Cc1c(C(=O)C(N)=O)c2c(OC(C)C(=O)O)cccc2n1Cc1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-12db1c229b3e4b39a2073d2783627aeb
COc1cccc2c1cc(C)n2Cc1ccccc1-c1ccccc1>>Cc1cc2c(O)cccc2n1Cc1ccccc1-c1ccccc1
C1(=C(C=CC=C1)CN1C(=CC2=C(C=CC=C12)OC)C)C1=CC=CC=C1.ClCl>>C1(=C(C=CC=C1)CN1C(=CC2=C(C=CC=C12)O)C)C1=CC=CC=C1
C[O:6][c:5]1[c:4]2[cH:3][c:2]([CH3:1])[n:11]([CH2:12][c:13]3[cH:14][cH:15][cH:16][cH:17][c:18]3-[c:19]3[cH:20][cH:21][cH:22][cH:23][cH:24]3)[c:10]2[cH:9][cH:8][cH:7]1>>[CH3:1][c:2]1[cH:3][c:4]2[c:5]([OH:6])[cH:7][cH:8][cH:9][c:10]2[n:11]1[CH2:12][c:13]1[cH:14][cH:15][cH:16][cH:17][c:18]1-[c:19]1[cH:20][cH:21][cH:22][cH...
COc1cccc2c1cc(C)n2Cc1ccccc1-c1ccccc1
Cc1cc2c(O)cccc2n1Cc1ccccc1-c1ccccc1
null
null
B(Br)(Br)Br
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc(-c2ccccc2Cn2ccc3ccccc32)cc1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]:[c:5]:[#7;a:6]>>[#7;a:6]:[c:5]:[c:4]:[c:2](-[OH;D1;+0:1]):[c:3]
55
[{"value": 55.0, "product": "C1(=C(C=CC=C1)CN1C(=CC2=C(C=CC=C12)O)C)C1=CC=CC=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 54.8, "product": "C1(=C(C=CC=C1)CN1C(=CC2=C(C=CC=C12)O)C)C1=CC=CC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
By the method used in Example 1, Part D, 1.6 g (4.9 mmol) of 1-([1,1'-biphenyl]-2-ylmethyl)-4-methoxy-2-methyl-1H-indole was O-demethylated by treating it with 20 mL of 1M BBr3 /CH2 Cl2. The crude product was chromatographed on silica gel and eluted with 20% EtOAc/hexane to give 841 mg (55% yield) of 1-([1,1'-biPhenyl]...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1cc2ccccc2[nH]1.c1ccccc1.c1ccccc1
Other
B(Br)(Br)Br
null
null
COc1cccc2c1cc(C)n2Cc1ccccc1-c1ccccc1>B(Br)(Br)Br>Cc1cc2c(O)cccc2n1Cc1ccccc1-c1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-574ffbc7e9b946328651db22944d9135
COC(=O)CBr.Cc1cc2c(O)cccc2n1Cc1ccccc1-c1ccccc1>>COC(=O)COc1cccc2c1cc(C)n2Cc1ccccc1-c1ccccc1
C1(=C(C=CC=C1)CN1C(=CC2=C(C=CC=C12)O)C)C1=CC=CC=C1.BrCC(=O)OC.[H-].[Na+]>>COC(COC1=C2C=C(N(C2=CC=C1)CC1=C(C=CC=C1)C1=CC=CC=C1)C)=O
Br[CH2:5][C:3]([O:2][CH3:1])=[O:4].[OH:6][c:7]1[cH:8][cH:9][cH:10][c:11]2[c:12]1[cH:13][c:14]([CH3:15])[n:16]2[CH2:17][c:18]1[cH:19][cH:20][cH:21][cH:22][c:23]1-[c:24]1[cH:25][cH:26][cH:27][cH:28][cH:29]1>>[CH3:1][O:2][C:3](=[O:4])[CH2:5][O:6][c:7]1[cH:8][cH:9][cH:10][c:11]2[c:12]1[cH:13][c:14]([CH3:15])[n:16]2[CH2:17]...
COC(=O)CBr.Cc1cc2c(O)cccc2n1Cc1ccccc1-c1ccccc1
COC(=O)COc1cccc2c1cc(C)n2Cc1ccccc1-c1ccccc1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
50d675b335c583a6ce22e1164b27a78b18b9ca447d45137820c344bcb6369217
0865de4e1853c59ac25437e36fd18b03329566cb9eff4b4f0ce70d5714692fd3
c1ccc(-c2ccccc2Cn2ccc3ccccc32)cc1
Br-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5].[#7;a:6]:[c:7]:[c:8]:[c:9](-[OH;D1;+0:10]):[c:11]>>[#7;a:6]:[c:7]:[c:8]:[c:9](-[O;H0;D2;+0:10]-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5]):[c:11]
77.3
[{"value": 77.0, "product": "COC(COC1=C2C=C(N(C2=CC=C1)CC1=C(C=CC=C1)C1=CC=CC=C1)C)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 77.3, "product": "COC(COC1=C2C=C(N(C2=CC=C1)CC1=C(C=CC=C1)C1=CC=CC=C1)C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
1-([1,1'-Biphenyl]-2-ylmethyl)-4-hydroxy-2-methyl-1H-indole (767 mg, 2.45 mmol) was alkylated by treating with 0.23 mL (2.45 mmol) of methyl bromoacetate and 98 mg (2.45 mmol) of 60% NaH/mineral oil in DMF as described in Example 1, Part E. The product was purified by chromatography over silica gel eluting with 20% EtO...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester.Aromatic alcohol
Ester.Ether
null
null
c1cc2ccccc2[nH]1.c1ccccc1.c1ccccc1
HBr
CN(C)C=O
null
null
COC(=O)CBr.Cc1cc2c(O)cccc2n1Cc1ccccc1-c1ccccc1>CN(C)C=O>COC(=O)COc1cccc2c1cc(C)n2Cc1ccccc1-c1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-47a003f9624147efadac55f5c60b94a3
COC(=O)COc1cccc2c1c(C(=O)C(N)=O)c(C)n2Cc1ccccc1-c1ccccc1>>Cc1c(C(=O)C(N)=O)c2c(OCC(=O)O)cccc2n1Cc1ccccc1-c1ccccc1
COC(COC1=C2C(=C(N(C2=CC=C1)CC1=C(C=CC=C1)C1=CC=CC=C1)C)C(C(=O)N)=O)=O.[Na]>>NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=C(C=CC=C1)C1=CC=CC=C1)C)=O
C[O:15][C:13]([CH2:12][O:11][c:10]1[c:9]2[c:3]([C:4](=[O:5])[C:6]([NH2:7])=[O:8])[c:2]([CH3:1])[n:20]([CH2:21][c:22]3[cH:23][cH:24][cH:25][cH:26][c:27]3-[c:28]3[cH:29][cH:30][cH:31][cH:32][cH:33]3)[c:19]2[cH:18][cH:17][cH:16]1)=[O:14]>>[CH3:1][c:2]1[c:3]([C:4](=[O:5])[C:6]([NH2:7])=[O:8])[c:9]2[c:10]([O:11][CH2:12][C:1...
COC(=O)COc1cccc2c1c(C(=O)C(N)=O)c(C)n2Cc1ccccc1-c1ccccc1
Cc1c(C(=O)C(N)=O)c2c(OCC(=O)O)cccc2n1Cc1ccccc1-c1ccccc1
null
null
[OH-].[Na+].CO
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1ccc(-c2ccccc2Cn2ccc3ccccc32)cc1
C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
36.6
[{"value": 35.0, "product": "NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=C(C=CC=C1)C1=CC=CC=C1)C)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 36.6, "product": "NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=C(C=CC=C1)C1=CC=CC=C1)C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
0.5
HOUR
A mixture of 648 mg (1.4 mmol) of [[3-(2-amino-1,2-dioxoethyl)-1-([1,1'-biphenyl]-2-ylmethyl)-2-methyl-1H-indol-4-yl]oxy]acetic acid methyl ester in 10 mL of 1N NaOH and 20 mL of MeOH was heated to maintain reflux for 1 hour, cooled to room temperature and stirred 0.5 hour. The mixture was concentrated, the residue sti...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1cc2ccccc2[nH]1.c1ccccc1.c1ccccc1
Other
[OH-].[Na+].CO
null
0.5
COC(=O)COc1cccc2c1c(C(=O)C(N)=O)c(C)n2Cc1ccccc1-c1ccccc1>[OH-].[Na+].CO>Cc1c(C(=O)C(N)=O)c2c(OCC(=O)O)cccc2n1Cc1ccccc1-c1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-5df3c79084144f99bcdc789e25be2a1e
COc1cccc2c1cc(C)n2Cc1cccc(-c2ccccc2)c1>>Cc1cc2c(O)cccc2n1Cc1cccc(-c2ccccc2)c1
C1(=CC(=CC=C1)CN1C(=CC2=C(C=CC=C12)OC)C)C1=CC=CC=C1.B(Br)(Br)Br.ClCl>>C1(=CC(=CC=C1)CN1C(=CC2=C(C=CC=C12)O)C)C1=CC=CC=C1
C[O:6][c:5]1[c:4]2[cH:3][c:2]([CH3:1])[n:11]([CH2:12][c:13]3[cH:14][cH:15][cH:16][c:17](-[c:18]4[cH:19][cH:20][cH:21][cH:22][cH:23]4)[cH:24]3)[c:10]2[cH:9][cH:8][cH:7]1>>[CH3:1][c:2]1[cH:3][c:4]2[c:5]([OH:6])[cH:7][cH:8][cH:9][c:10]2[n:11]1[CH2:12][c:13]1[cH:14][cH:15][cH:16][c:17](-[c:18]2[cH:19][cH:20][cH:21][cH:22][...
COc1cccc2c1cc(C)n2Cc1cccc(-c2ccccc2)c1
Cc1cc2c(O)cccc2n1Cc1cccc(-c2ccccc2)c1
null
null
null
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc(-c2cccc(Cn3ccc4ccccc43)c2)cc1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]:[c:5]:[#7;a:6]>>[#7;a:6]:[c:5]:[c:4]:[c:2](-[OH;D1;+0:1]):[c:3]
87
[{"value": 87.0, "product": "C1(=CC(=CC=C1)CN1C(=CC2=C(C=CC=C12)O)C)C1=CC=CC=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 86.5, "product": "C1(=CC(=CC=C1)CN1C(=CC2=C(C=CC=C12)O)C)C1=CC=CC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
By the method used in Example 1, Part D, 1.25 g (3.8 mmol) of 1-([1,1'-biphenyl]-3-ylmethyl)-4-methoxy-2-methyl-1H-indole was O-demethylated by treating it with 15.2 mL of 1M BBr3 /CH2 Cl2 to give 1.03 g (87% yield) of crude 1-([1,1'-biphenyl]-3-ylmethyl)-4-hydroxy-2-methyl-1H-indole. Conditions: See reaction.notes.pro...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1cc2ccccc2[nH]1.c1ccccc1.c1ccccc1
Other
null
null
null
COc1cccc2c1cc(C)n2Cc1cccc(-c2ccccc2)c1>>Cc1cc2c(O)cccc2n1Cc1cccc(-c2ccccc2)c1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-ddd7e0bd7cef44e8b59de3a93c55dc2b
COC(=O)CBr.Cc1cc2c(O)cccc2n1Cc1cccc(-c2ccccc2)c1>>COC(=O)COc1cccc2c1cc(C)n2Cc1cccc(-c2ccccc2)c1
C1(=CC(=CC=C1)CN1C(=CC2=C(C=CC=C12)O)C)C1=CC=CC=C1.BrCC(=O)OC.[H-].[Na+]>>COC(COC1=C2C=C(N(C2=CC=C1)CC=1C=C(C=CC1)C1=CC=CC=C1)C)=O
Br[CH2:5][C:3]([O:2][CH3:1])=[O:4].[OH:6][c:7]1[cH:8][cH:9][cH:10][c:11]2[c:12]1[cH:13][c:14]([CH3:15])[n:16]2[CH2:17][c:18]1[cH:19][cH:20][cH:21][c:22](-[c:23]2[cH:24][cH:25][cH:26][cH:27][cH:28]2)[cH:29]1>>[CH3:1][O:2][C:3](=[O:4])[CH2:5][O:6][c:7]1[cH:8][cH:9][cH:10][c:11]2[c:12]1[cH:13][c:14]([CH3:15])[n:16]2[CH2:1...
COC(=O)CBr.Cc1cc2c(O)cccc2n1Cc1cccc(-c2ccccc2)c1
COC(=O)COc1cccc2c1cc(C)n2Cc1cccc(-c2ccccc2)c1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
50d675b335c583a6ce22e1164b27a78b18b9ca447d45137820c344bcb6369217
0865de4e1853c59ac25437e36fd18b03329566cb9eff4b4f0ce70d5714692fd3
c1ccc(-c2cccc(Cn3ccc4ccccc43)c2)cc1
Br-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5].[#7;a:6]:[c:7]:[c:8]:[c:9](-[OH;D1;+0:10]):[c:11]>>[#7;a:6]:[c:7]:[c:8]:[c:9](-[O;H0;D2;+0:10]-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5]):[c:11]
79
[{"value": 79.0, "product": "COC(COC1=C2C=C(N(C2=CC=C1)CC=1C=C(C=CC1)C1=CC=CC=C1)C)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 78.6, "product": "COC(COC1=C2C=C(N(C2=CC=C1)CC=1C=C(C=CC1)C1=CC=CC=C1)C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
1-([1,1'-Biphenyl]-3-ylmethyl)-4-hydroxy-2-methyl-1H-indole (1.03 g, 3.3 mmol) was alkylated by treating with 0.31 mL (3.3 mmol) of methyl bromoacetate and 132 mg (3.3 mmol) of 60% NaH/mineral oil in DMF as described in Example 1, Part E. The product was purified by chromatography over silica gel eluting with 20% EtOAc...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester.Aromatic alcohol
Ester.Ether
null
null
c1cc2ccccc2[nH]1.c1ccccc1.c1ccccc1
HBr
CN(C)C=O
null
null
COC(=O)CBr.Cc1cc2c(O)cccc2n1Cc1cccc(-c2ccccc2)c1>CN(C)C=O>COC(=O)COc1cccc2c1cc(C)n2Cc1cccc(-c2ccccc2)c1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-a59e6c8dd5fb48dda0e37c75c7c2b042
COc1cccc2c1cc(C)n2Cc1ccc(-c2ccccc2)cc1>>Cc1cc2c(O)cccc2n1Cc1ccc(-c2ccccc2)cc1
C1(=CC=C(C=C1)CN1C(=CC2=C(C=CC=C12)OC)C)C1=CC=CC=C1.B(Br)(Br)Br.ClCl>>C1(=CC=C(C=C1)CN1C(=CC2=C(C=CC=C12)O)C)C1=CC=CC=C1
C[O:6][c:5]1[c:4]2[cH:3][c:2]([CH3:1])[n:11]([CH2:12][c:13]3[cH:14][cH:15][c:16](-[c:17]4[cH:18][cH:19][cH:20][cH:21][cH:22]4)[cH:23][cH:24]3)[c:10]2[cH:9][cH:8][cH:7]1>>[CH3:1][c:2]1[cH:3][c:4]2[c:5]([OH:6])[cH:7][cH:8][cH:9][c:10]2[n:11]1[CH2:12][c:13]1[cH:14][cH:15][c:16](-[c:17]2[cH:18][cH:19][cH:20][cH:21][cH:22]2...
COc1cccc2c1cc(C)n2Cc1ccc(-c2ccccc2)cc1
Cc1cc2c(O)cccc2n1Cc1ccc(-c2ccccc2)cc1
null
null
null
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc(-c2ccc(Cn3ccc4ccccc43)cc2)cc1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]:[c:5]:[#7;a:6]>>[#7;a:6]:[c:5]:[c:4]:[c:2](-[OH;D1;+0:1]):[c:3]
77.4
[{"value": 77.0, "product": "C1(=CC=C(C=C1)CN1C(=CC2=C(C=CC=C12)O)C)C1=CC=CC=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 77.4, "product": "C1(=CC=C(C=C1)CN1C(=CC2=C(C=CC=C12)O)C)C1=CC=CC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
By the method used in Example 1, Part D, 1.3 g (4.0 mmol) of 1-([1,1'-biphenyl]-4-ylmethyl)-4-methoxy-2-methyl-1H-indole was O-demethylated by treating it with 16 mL of 1M BBr3 /CH2 Cl2 to give 970 mg (77% yield) of crude 1-([1,1'-biphenyl]-4-ylmethyl)-4-hydroxy-2-methyl-1H-indole. Conditions: See reaction.notes.proced...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1cc2ccccc2[nH]1.c1ccccc1.c1ccccc1
Other
null
null
null
COc1cccc2c1cc(C)n2Cc1ccc(-c2ccccc2)cc1>>Cc1cc2c(O)cccc2n1Cc1ccc(-c2ccccc2)cc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-6e4a7111550b4748814745d936cdc81f
COC(=O)CBr.Cc1cc2c(O)cccc2n1Cc1cccc(-c2ccccc2)c1>>COC(=O)COc1cccc2c1cc(C)n2Cc1ccc(-c2ccccc2)cc1
C1(=CC(=CC=C1)CN1C(=CC2=C(C=CC=C12)O)C)C1=CC=CC=C1.[H-].[Na+].BrCC(=O)OC>>COC(COC1=C2C=C(N(C2=CC=C1)CC1=CC=C(C=C1)C1=CC=CC=C1)C)=O
Br[CH2:5][C:3]([O:2][CH3:1])=[O:4].[OH:6][c:7]1[cH:8][cH:9][cH:10][c:11]2[c:12]1[cH:13][c:14]([CH3:15])[n:16]2[CH2:17][c:18]1[cH:19][cH:20][cH:28][c:21](-[c:22]2[cH:23][cH:24][cH:25][cH:26][cH:27]2)[cH:29]1>>[CH3:1][O:2][C:3](=[O:4])[CH2:5][O:6][c:7]1[cH:8][cH:9][cH:10][c:11]2[c:12]1[cH:13][c:14]([CH3:15])[n:16]2[CH2:1...
COC(=O)CBr.Cc1cc2c(O)cccc2n1Cc1cccc(-c2ccccc2)c1
COC(=O)COc1cccc2c1cc(C)n2Cc1ccc(-c2ccccc2)cc1
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
7b00df63d7ae8680effc7ac2209a8a71eb4af9dc74b8220117411a77e22c75ef
0865de4e1853c59ac25437e36fd18b03329566cb9eff4b4f0ce70d5714692fd3
c1ccc(-c2ccc(Cn3ccc4ccccc43)cc2)cc1
Br-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5].[OH;D1;+0:6]-[c:7](:[c:8]):[c:9]:[c:10]:[#7;a:11]-[C:12]-[c:13]1:[c:14]:[cH;D2;+0:15]:[cH;D2;+0:16]:[c;H0;D3;+0:17](-[c:18](:[c:19]):[c:20]):[cH;D2;+0:21]:1>>[C;D1;H3:5]-[#8:4]-[C:2](=[O;D1;H0:3])-[CH2;D2;+0:1]-[O;H0;D2;+0:6]-[c:7](:[c:8]):[c:9]:[c:10]:[#7;a:11]-[...
125
[{"value": 63.0, "product": "COC(COC1=C2C=C(N(C2=CC=C1)CC1=CC=C(C=C1)C1=CC=CC=C1)C)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 125.0, "product": "COC(COC1=C2C=C(N(C2=CC=C1)CC1=CC=C(C=C1)C1=CC=CC=C1)C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using the procedure described in Example 1, Part E, 1-([1,1'-biphenyl]-3-ylmethyl)-4-hydroxy-2-methyl-1H-indole (970 mg, 3.1 mmol) was treated with 124 mg (3.1 mmol) of 60% NaH/mineral oil and then 0.29 mL (3.1 mmol) of methyl bromoacetate. The product was purified by chromatography over silica gel eluting with 20% EtO...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester.Aromatic alcohol
Ester.Ether
c1ccccc1
c1ccccc1
c1cc2ccccc2[nH]1.c1ccccc1.c1ccccc1
HBr
null
null
null
COC(=O)CBr.Cc1cc2c(O)cccc2n1Cc1cccc(-c2ccccc2)c1>>COC(=O)COc1cccc2c1cc(C)n2Cc1ccc(-c2ccccc2)cc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-2430659498234afdad6429ef09e67331
COC(=O)COc1cccc2c1c(C(=O)C(N)=O)c(C)n2Cc1ccc(-c2ccccc2)cc1>>Cc1c(C(=O)C(N)=O)c2c(OCC(=O)O)cccc2n1Cc1ccc(-c2ccccc2)cc1
COC(COC1=C2C(=C(N(C2=CC=C1)CC1=CC=C(C=C1)C1=CC=CC=C1)C)C(C(=O)N)=O)=O.CO.[Na]>>NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=CC=C(C=C1)C1=CC=CC=C1)C)=O
C[O:15][C:13]([CH2:12][O:11][c:10]1[c:9]2[c:3]([C:4](=[O:5])[C:6]([NH2:7])=[O:8])[c:2]([CH3:1])[n:20]([CH2:21][c:22]3[cH:23][cH:24][c:25](-[c:26]4[cH:27][cH:28][cH:29][cH:30][cH:31]4)[cH:32][cH:33]3)[c:19]2[cH:18][cH:17][cH:16]1)=[O:14]>>[CH3:1][c:2]1[c:3]([C:4](=[O:5])[C:6]([NH2:7])=[O:8])[c:9]2[c:10]([O:11][CH2:12][C...
COC(=O)COc1cccc2c1c(C(=O)C(N)=O)c(C)n2Cc1ccc(-c2ccccc2)cc1
Cc1c(C(=O)C(N)=O)c2c(OCC(=O)O)cccc2n1Cc1ccc(-c2ccccc2)cc1
null
null
[OH-].[Na+]
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1ccc(-c2ccc(Cn3ccc4ccccc43)cc2)cc1
C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
77.1
[{"value": 74.0, "product": "NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=CC=C(C=C1)C1=CC=CC=C1)C)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 77.1, "product": "NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=CC=C(C=C1)C1=CC=CC=C1)C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using the procedure described in Example 2, Part E, 803 mg (1.8 mmol) of [[3-(2-amino-1,2-dioxoethyl)-1-([1,1'-biphenyl]-4-ylmethyl)-2-methyl-1H-indol-4-yl]oxy]acetic acid methyl ester was hydrolyzed in 10 mL of 1N NaOH and 20 mL of MeOH to give 614 mg (74% yield) of [[3-(2-amino-1,2-dioxoethyl)-1-([1,1'-biphenyl]-4-yl...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1cc2ccccc2[nH]1.c1ccccc1.c1ccccc1
Other
[OH-].[Na+]
null
null
COC(=O)COc1cccc2c1c(C(=O)C(N)=O)c(C)n2Cc1ccc(-c2ccccc2)cc1>[OH-].[Na+]>Cc1c(C(=O)C(N)=O)c2c(OCC(=O)O)cccc2n1Cc1ccc(-c2ccccc2)cc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-996f0a7d980d4f7db95b5a7e4dbfa2a5
COc1cccc2c1cc(C)n2Cc1c(Cl)cccc1Cl>>Cc1cc2c(O)cccc2n1Cc1c(Cl)cccc1Cl
ClC1=C(C(=CC=C1)Cl)CN1C(=CC2=C(C=CC=C12)OC)C.B(Br)(Br)Br.C(Cl)Cl>>ClC1=C(C(=CC=C1)Cl)CN1C(=CC2=C(C=CC=C12)O)C
C[O:6][c:5]1[c:4]2[cH:3][c:2]([CH3:1])[n:11]([CH2:12][c:13]3[c:14]([Cl:15])[cH:16][cH:17][cH:18][c:19]3[Cl:20])[c:10]2[cH:9][cH:8][cH:7]1>>[CH3:1][c:2]1[cH:3][c:4]2[c:5]([OH:6])[cH:7][cH:8][cH:9][c:10]2[n:11]1[CH2:12][c:13]1[c:14]([Cl:15])[cH:16][cH:17][cH:18][c:19]1[Cl:20]
COc1cccc2c1cc(C)n2Cc1c(Cl)cccc1Cl
Cc1cc2c(O)cccc2n1Cc1c(Cl)cccc1Cl
null
null
null
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc(Cn2ccc3ccccc32)cc1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]:[c:5]:[#7;a:6]>>[#7;a:6]:[c:5]:[c:4]:[c:2](-[OH;D1;+0:1]):[c:3]
83.3
[{"value": 83.0, "product": "ClC1=C(C(=CC=C1)Cl)CN1C(=CC2=C(C=CC=C12)O)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 83.3, "product": "ClC1=C(C(=CC=C1)Cl)CN1C(=CC2=C(C=CC=C12)O)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
By the method used in Example 1, Part D, 1.08 g (3.38 mmol) of 1-[(2,6 dichlorophenyl)methyl]-4-methoxy-2-methyl-1H-indole was O-demethylated by treating it with 13.5 mL of 1M BBr3 /CH2Cl2 to give 862 mg (83% yield) of 1-[(2,6-dichlorophenyl)methyl]-4-hydroxy-2-methyl-1H-indole, after chromatography on silica gel (elut...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1cc2ccccc2[nH]1.c1ccccc1
Other
null
null
null
COc1cccc2c1cc(C)n2Cc1c(Cl)cccc1Cl>>Cc1cc2c(O)cccc2n1Cc1c(Cl)cccc1Cl
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-3d65a4f4324145edb476d47530c4a7b6
COC(=O)CBr.Cc1cc2c(O)cccc2n1Cc1c(Cl)cccc1Cl>>COC(=O)COc1cccc2c1cc(C)n2Cc1c(Cl)cccc1Cl
ClC1=C(C(=CC=C1)Cl)CN1C(=CC2=C(C=CC=C12)O)C.[H-].[Na+].BrCC(=O)OC>>COC(COC1=C2C=C(N(C2=CC=C1)CC1=C(C=CC=C1Cl)Cl)C)=O
Br[CH2:5][C:3]([O:2][CH3:1])=[O:4].[OH:6][c:7]1[cH:8][cH:9][cH:10][c:11]2[c:12]1[cH:13][c:14]([CH3:15])[n:16]2[CH2:17][c:18]1[c:19]([Cl:20])[cH:21][cH:22][cH:23][c:24]1[Cl:25]>>[CH3:1][O:2][C:3](=[O:4])[CH2:5][O:6][c:7]1[cH:8][cH:9][cH:10][c:11]2[c:12]1[cH:13][c:14]([CH3:15])[n:16]2[CH2:17][c:18]1[c:19]([Cl:20])[cH:21]...
COC(=O)CBr.Cc1cc2c(O)cccc2n1Cc1c(Cl)cccc1Cl
COC(=O)COc1cccc2c1cc(C)n2Cc1c(Cl)cccc1Cl
null
null
null
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
50d675b335c583a6ce22e1164b27a78b18b9ca447d45137820c344bcb6369217
0865de4e1853c59ac25437e36fd18b03329566cb9eff4b4f0ce70d5714692fd3
c1ccc(Cn2ccc3ccccc32)cc1
Br-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5].[#7;a:6]:[c:7]:[c:8]:[c:9](-[OH;D1;+0:10]):[c:11]>>[#7;a:6]:[c:7]:[c:8]:[c:9](-[O;H0;D2;+0:10]-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5]):[c:11]
39
[{"value": 39.0, "product": "COC(COC1=C2C=C(N(C2=CC=C1)CC1=C(C=CC=C1Cl)Cl)C)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 38.8, "product": "COC(COC1=C2C=C(N(C2=CC=C1)CC1=C(C=CC=C1Cl)Cl)C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using the procedure described in Example 1, Part E, 1-[(2,6-dichlorophenyl)methyl]-4-hydroxy-2-methyl-1H-indole (862 mg, 2.8 mmol) was treated with 112 mg (2.8 mmol) of 60% NaH/mineral oil and then 0.27 mL (2.8 mmol) of methyl bromoacetate. The product was purified by chromatography over silica gel eluting with 20% EtO...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester.Aromatic alcohol
Ester.Ether
null
null
c1cc2ccccc2[nH]1.c1ccccc1
HBr
null
null
null
COC(=O)CBr.Cc1cc2c(O)cccc2n1Cc1c(Cl)cccc1Cl>>COC(=O)COc1cccc2c1cc(C)n2Cc1c(Cl)cccc1Cl
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-06734e09bf9f433d9b3795926278123c
COC(=O)COc1cccc2c1c(C(=O)C(N)=O)c(C)n2Cc1c(Cl)cccc1Cl>>Cc1c(C(=O)C(N)=O)c2c(OCC(=O)O)cccc2n1Cc1c(Cl)cccc1Cl
COC(COC1=C2C(=C(N(C2=CC=C1)CC1=C(C=CC=C1Cl)Cl)C)C(C(=O)N)=O)=O.[OH-].[Na+].CO.C(C)(=O)OCC>>NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=C(C=CC=C1Cl)Cl)C)=O
C[O:15][C:13]([CH2:12][O:11][c:10]1[c:9]2[c:3]([C:4](=[O:5])[C:6]([NH2:7])=[O:8])[c:2]([CH3:1])[n:20]([CH2:21][c:22]3[c:23]([Cl:24])[cH:25][cH:26][cH:27][c:28]3[Cl:29])[c:19]2[cH:18][cH:17][cH:16]1)=[O:14]>>[CH3:1][c:2]1[c:3]([C:4](=[O:5])[C:6]([NH2:7])=[O:8])[c:9]2[c:10]([O:11][CH2:12][C:13](=[O:14])[OH:15])[cH:16][cH...
COC(=O)COc1cccc2c1c(C(=O)C(N)=O)c(C)n2Cc1c(Cl)cccc1Cl
Cc1c(C(=O)C(N)=O)c2c(OCC(=O)O)cccc2n1Cc1c(Cl)cccc1Cl
null
null
O
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1ccc(Cn2ccc3ccccc32)cc1
C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
86
[{"value": 86.0, "product": "NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=C(C=CC=C1Cl)Cl)C)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 85.8, "product": "NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=C(C=CC=C1Cl)Cl)C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
0.5
HOUR
A mixture of 420 mg (0.94 mmol) of [[3-(2-amino-1,2-dioxoethyl)-1-[(2,6-dichlorophenyl)methyl]-2-methyl-1H-indol-4-yl]oxy]acetic acid methyl ester, 5 mL of 1N NaOH and 15 mL of MeOH was heated to maintain reflux for 0.17 hours, cooled to room temperature and stirred 0.5 hours. Ethyl acetate and water was added, the aqu...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1cc2ccccc2[nH]1.c1ccccc1
Other
O
null
0.5
COC(=O)COc1cccc2c1c(C(=O)C(N)=O)c(C)n2Cc1c(Cl)cccc1Cl>O>Cc1c(C(=O)C(N)=O)c2c(OCC(=O)O)cccc2n1Cc1c(Cl)cccc1Cl
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-69862c99df73480e9bc323a291044204
COc1cccc2[nH]c(C)cc12.Fc1ccc(CCl)cc1>>COc1cccc2c1cc(C)n2Cc1ccc(F)cc1
FC1=CC=C(CCl)C=C1.COC1=C2C=C(NC2=CC=C1)C.[H-].[Na+].CCCCCC>>FC1=CC=C(C=C1)CN1C(=CC2=C(C=CC=C12)OC)C
[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][c:7]2[c:8]1[cH:9][c:10]([CH3:11])[nH:12]2.Cl[CH2:13][c:14]1[cH:15][cH:16][c:17]([F:18])[cH:19][cH:20]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][c:7]2[c:8]1[cH:9][c:10]([CH3:11])[n:12]2[CH2:13][c:14]1[cH:15][cH:16][c:17]([F:18])[cH:19][cH:20]1
COc1cccc2[nH]c(C)cc12.Fc1ccc(CCl)cc1
COc1cccc2c1cc(C)n2Cc1ccc(F)cc1
null
null
CN(C)C=O.O
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
16b46a8af20339f7ff0b611b4ac5dd01fe35ba577361e893c359dfa478dc1974
2e1e5fd9557b69cb528f6b2ffd179c67ef24ecb1a2c3994e1cdf0efe7ae19e9c
c1ccc(Cn2ccc3ccccc32)cc1
Cl-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[C;D1;H3:5]-[c:6]1:[c:7]:[c:8]:[c:9](:[c:10]):[nH;D2;+0:11]:1>>[C;D1;H3:5]-[c:6]1:[c:7]:[c:8]:[c:9](:[c:10]):[n;H0;D3;+0:11]:1-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4]
84
[{"value": 84.0, "product": "FC1=CC=C(C=C1)CN1C(=CC2=C(C=CC=C12)OC)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 81.7, "product": "FC1=CC=C(C=C1)CN1C(=CC2=C(C=CC=C12)OC)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
0.5
HOUR
4-Methoxy-2-methyl-1H-indole (805 mg, 5 mmol) was added to a mixture of 200 mg (5 mmol) of 60% sodium hydride/mineral oil (washed with hexane before adding DMF) in 10 mL of DMF and after stirring for 0.5 hours, 0.6 mL (5 mmol) of 4-fluorobenzyl chloride was added. The mixture was stirred at room temperature for 18 hour...
10.6084/m9.figshare.5104873.v1
null
Primary halide
null
c1ccc2[nH]ccc2c1
c1cc2ccccc2[nH]1
c1cc2ccccc2[nH]1.c1ccccc1
HCl
CN(C)C=O.O
null
0.5
COc1cccc2[nH]c(C)cc12.Fc1ccc(CCl)cc1>CN(C)C=O.O>COc1cccc2c1cc(C)n2Cc1ccc(F)cc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-858e366b919f470e923529fff24917ea
COc1cccc2c1cc(C)n2Cc1ccc(F)cc1>>Cc1cc2c(O)cccc2n1Cc1ccc(F)cc1
FC1=CC=C(C=C1)CN1C(=CC2=C(C=CC=C12)OC)C.B(Br)(Br)Br.C(Cl)Cl>>FC1=CC=C(C=C1)CN1C(=CC2=C(C=CC=C12)O)C
C[O:6][c:5]1[c:4]2[cH:3][c:2]([CH3:1])[n:11]([CH2:12][c:13]3[cH:14][cH:15][c:16]([F:17])[cH:18][cH:19]3)[c:10]2[cH:9][cH:8][cH:7]1>>[CH3:1][c:2]1[cH:3][c:4]2[c:5]([OH:6])[cH:7][cH:8][cH:9][c:10]2[n:11]1[CH2:12][c:13]1[cH:14][cH:15][c:16]([F:17])[cH:18][cH:19]1
COc1cccc2c1cc(C)n2Cc1ccc(F)cc1
Cc1cc2c(O)cccc2n1Cc1ccc(F)cc1
null
null
null
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc(Cn2ccc3ccccc32)cc1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]:[c:5]:[#7;a:6]>>[#7;a:6]:[c:5]:[c:4]:[c:2](-[OH;D1;+0:1]):[c:3]
84.2
[{"value": 84.0, "product": "FC1=CC=C(C=C1)CN1C(=CC2=C(C=CC=C12)O)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 84.2, "product": "FC1=CC=C(C=C1)CN1C(=CC2=C(C=CC=C12)O)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
By the method used in Example 1, Part D, 1.1 g (4.1 mmol) of 1-[(4-fluorophenyl)methyl]-4-methoxy-2-methyl-1H-indole was O-demethylated by treating it with 16.4 mL of 1M BBr3 /CH2Cl2 to give 881 mg (84% yield) of crude 1-[(4-fluorophenyl)methyl]-4-hydroxy-2-methyl-1H-indole. Conditions: See reaction.notes.procedure_det...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1cc2ccccc2[nH]1.c1ccccc1
Other
null
null
null
COc1cccc2c1cc(C)n2Cc1ccc(F)cc1>>Cc1cc2c(O)cccc2n1Cc1ccc(F)cc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-b5b468e495014e1391684d9a81922ee1
COC(=O)CBr.Cc1cc2c(O)cccc2n1Cc1ccc(F)cc1>>COC(=O)COc1cccc2c1cc(C)n2Cc1ccc(F)cc1
FC1=CC=C(C=C1)CN1C(=CC2=C(C=CC=C12)O)C.[H-].[Na+].BrCC(=O)OC>>COC(COC1=C2C=C(N(C2=CC=C1)CC1=CC=C(C=C1)F)C)=O
Br[CH2:5][C:3]([O:2][CH3:1])=[O:4].[OH:6][c:7]1[cH:8][cH:9][cH:10][c:11]2[c:12]1[cH:13][c:14]([CH3:15])[n:16]2[CH2:17][c:18]1[cH:19][cH:20][c:21]([F:22])[cH:23][cH:24]1>>[CH3:1][O:2][C:3](=[O:4])[CH2:5][O:6][c:7]1[cH:8][cH:9][cH:10][c:11]2[c:12]1[cH:13][c:14]([CH3:15])[n:16]2[CH2:17][c:18]1[cH:19][cH:20][c:21]([F:22])[...
COC(=O)CBr.Cc1cc2c(O)cccc2n1Cc1ccc(F)cc1
COC(=O)COc1cccc2c1cc(C)n2Cc1ccc(F)cc1
null
null
null
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
50d675b335c583a6ce22e1164b27a78b18b9ca447d45137820c344bcb6369217
0865de4e1853c59ac25437e36fd18b03329566cb9eff4b4f0ce70d5714692fd3
c1ccc(Cn2ccc3ccccc32)cc1
Br-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5].[#7;a:6]:[c:7]:[c:8]:[c:9](-[OH;D1;+0:10]):[c:11]>>[#7;a:6]:[c:7]:[c:8]:[c:9](-[O;H0;D2;+0:10]-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5]):[c:11]
81
[{"value": 81.0, "product": "COC(COC1=C2C=C(N(C2=CC=C1)CC1=CC=C(C=C1)F)C)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 80.9, "product": "COC(COC1=C2C=C(N(C2=CC=C1)CC1=CC=C(C=C1)F)C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using the procedure described in Example 1, Part E, 1-[(4-fluorophenyl)methyl]-4-hydroxy-2-methyl-1H-indole (881 mg, 3.45 mmol) was treated with 138 mg (3.45 mmol) of 60% NaH/mineral oil and then 0.33 mL (3.45 mmol) of methyl bromoacetate. The product was purified by chromatography over silica gel eluting with 20% EtOA...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester.Aromatic alcohol
Ester.Ether
null
null
c1cc2ccccc2[nH]1.c1ccccc1
HBr
null
null
null
COC(=O)CBr.Cc1cc2c(O)cccc2n1Cc1ccc(F)cc1>>COC(=O)COc1cccc2c1cc(C)n2Cc1ccc(F)cc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-1f91a3ebc06246c6a616154657ef7250
COC(=O)COc1cccc2c1c(C(=O)C(N)=O)c(C)n2Cc1ccc(F)cc1>>Cc1c(C(=O)C(N)=O)c2c(OCC(=O)O)cccc2n1Cc1ccc(F)cc1
COC(COC1=C2C(=C(N(C2=CC=C1)CC1=CC=C(C=C1)F)C)C(C(=O)N)=O)=O.[OH-].[Na+].CO.C(C)(=O)OCC>>NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=CC=C(C=C1)F)C)=O
C[O:15][C:13]([CH2:12][O:11][c:10]1[c:9]2[c:3]([C:4](=[O:5])[C:6]([NH2:7])=[O:8])[c:2]([CH3:1])[n:20]([CH2:21][c:22]3[cH:23][cH:24][c:25]([F:26])[cH:27][cH:28]3)[c:19]2[cH:18][cH:17][cH:16]1)=[O:14]>>[CH3:1][c:2]1[c:3]([C:4](=[O:5])[C:6]([NH2:7])=[O:8])[c:9]2[c:10]([O:11][CH2:12][C:13](=[O:14])[OH:15])[cH:16][cH:17][cH...
COC(=O)COc1cccc2c1c(C(=O)C(N)=O)c(C)n2Cc1ccc(F)cc1
Cc1c(C(=O)C(N)=O)c2c(OCC(=O)O)cccc2n1Cc1ccc(F)cc1
null
null
O
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1ccc(Cn2ccc3ccccc32)cc1
C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
81.2
[{"value": 81.0, "product": "NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=CC=C(C=C1)F)C)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 81.2, "product": "NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=CC=C(C=C1)F)C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
A mixture of 767 mg (1.9 mmol) of [[3-(2-amino-1,2-dioxoethyl)-1-[(4-fluorophenyl)methyl]-2-methyl-1H-indol-4-yl]oxy]acetic acid methyl ester, 10 mL of 1N NaOH and 30 mL of MeOH was heated to maintain reflux for 0.67 hours, cooled to room temperature and stirred 1 hour. Ethyl acetate and water were added and the aqueou...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1cc2ccccc2[nH]1.c1ccccc1
Other
O
null
1
COC(=O)COc1cccc2c1c(C(=O)C(N)=O)c(C)n2Cc1ccc(F)cc1>O>Cc1c(C(=O)C(N)=O)c2c(OCC(=O)O)cccc2n1Cc1ccc(F)cc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-80c7b751a3284a8b966f0ea7134ae600
COc1cccc2[nH]c(C)cc12.ClCc1cccc2ccccc12>>COc1cccc2c1cc(C)n2Cc1cccc2ccccc12
COC1=C2C=C(NC2=CC=C1)C.[H-].[Na+].ClCC1=CC=CC2=CC=CC=C12>>COC1=C2C=C(N(C2=CC=C1)CC1=CC=CC2=CC=CC=C12)C
[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][c:7]2[c:8]1[cH:9][c:10]([CH3:11])[nH:12]2.Cl[CH2:13][c:14]1[cH:15][cH:16][cH:17][c:18]2[cH:19][cH:20][cH:21][cH:22][c:23]12>>[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][c:7]2[c:8]1[cH:9][c:10]([CH3:11])[n:12]2[CH2:13][c:14]1[cH:15][cH:16][cH:17][c:18]2[cH:19][cH:20][cH:21][cH:22][c:23]12
COc1cccc2[nH]c(C)cc12.ClCc1cccc2ccccc12
COc1cccc2c1cc(C)n2Cc1cccc2ccccc12
null
null
CN(C)C=O.O
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
16b46a8af20339f7ff0b611b4ac5dd01fe35ba577361e893c359dfa478dc1974
2e1e5fd9557b69cb528f6b2ffd179c67ef24ecb1a2c3994e1cdf0efe7ae19e9c
c1ccc2c(Cn3ccc4ccccc43)cccc2c1
Cl-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[C;D1;H3:5]-[c:6]1:[c:7]:[c:8]:[c:9](:[c:10]):[nH;D2;+0:11]:1>>[C;D1;H3:5]-[c:6]1:[c:7]:[c:8]:[c:9](:[c:10]):[n;H0;D3;+0:11]:1-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4]
97.1
[{"value": 97.0, "product": "COC1=C2C=C(N(C2=CC=C1)CC1=CC=CC2=CC=CC=C12)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 97.1, "product": "COC1=C2C=C(N(C2=CC=C1)CC1=CC=CC2=CC=CC=C12)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
0.67
HOUR
4-Methoxy-2-methyl-1H-indole (644 mg, 4 mmol) was dissolved in 10 mL of DMF and 160 mg (4 mmol) of 60% NaH/mineral oil was added. After 0.67 hours, 707 mg (4 mmol) of 1-(chloromethyl)naphthalene was added. After 5 hours, the mixture was diluted with water and extracted twice with ethyl acetate. The combined ethyl aceta...
10.6084/m9.figshare.5104873.v1
null
Primary halide
null
c1ccc2[nH]ccc2c1
c1cc2ccccc2[nH]1
c1cc2ccccc2[nH]1.c1ccc2ccccc2c1
HCl
CN(C)C=O.O
null
0.67
COc1cccc2[nH]c(C)cc12.ClCc1cccc2ccccc12>CN(C)C=O.O>COc1cccc2c1cc(C)n2Cc1cccc2ccccc12
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-ac45098226724296a2030ef33a83f824
COc1cccc2c1cc(C)n2Cc1cccc2ccccc12>>Cc1cc2c(O)cccc2n1Cc1cccc2ccccc12
COC1=C2C=C(N(C2=CC=C1)CC1=CC=CC2=CC=CC=C12)C.B(Br)(Br)Br.C(Cl)Cl>>OC1=C2C=C(N(C2=CC=C1)CC1=CC=CC2=CC=CC=C12)C
C[O:6][c:5]1[c:4]2[cH:3][c:2]([CH3:1])[n:11]([CH2:12][c:13]3[cH:14][cH:15][cH:16][c:17]4[cH:18][cH:19][cH:20][cH:21][c:22]34)[c:10]2[cH:9][cH:8][cH:7]1>>[CH3:1][c:2]1[cH:3][c:4]2[c:5]([OH:6])[cH:7][cH:8][cH:9][c:10]2[n:11]1[CH2:12][c:13]1[cH:14][cH:15][cH:16][c:17]2[cH:18][cH:19][cH:20][cH:21][c:22]12
COc1cccc2c1cc(C)n2Cc1cccc2ccccc12
Cc1cc2c(O)cccc2n1Cc1cccc2ccccc12
null
null
CCOC(=O)C.CCCCCC
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc2c(Cn3ccc4ccccc43)cccc2c1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]:[c:5]:[#7;a:6]>>[#7;a:6]:[c:5]:[c:4]:[c:2](-[OH;D1;+0:1]):[c:3]
71
[{"value": 71.0, "product": "OC1=C2C=C(N(C2=CC=C1)CC1=CC=CC2=CC=CC=C12)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 71.0, "product": "OC1=C2C=C(N(C2=CC=C1)CC1=CC=CC2=CC=CC=C12)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
By the method used in Example 1, Part D, 1.17 g (3.9 mmol) of 4-methoxy-2-methyl-1-[(1-naphthalenyl)methyl]-1H-indole was O-demethylated by treating it with 15.6 mL of 1M BBr3 /CH2Cl2 to give a material that was chromatographed on silica gel (eluted with 20% EtOAc/hexane then 50% EtOAc/hexane) to give 796 mg (71% yield...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1cc2ccccc2[nH]1.c1ccc2ccccc2c1
Other
CCOC(=O)C.CCCCCC
null
null
COc1cccc2c1cc(C)n2Cc1cccc2ccccc12>CCOC(=O)C.CCCCCC>Cc1cc2c(O)cccc2n1Cc1cccc2ccccc12
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-9be854f4426b4c0084e2dc374f4ca800
COC(=O)CBr.Cc1cc2c(O)cccc2n1Cc1cccc2ccccc12>>COC(=O)COc1cccc2c1cc(C)n2Cc1cccc2ccccc12
OC1=C2C=C(N(C2=CC=C1)CC1=CC=CC2=CC=CC=C12)C.[H-].[Na+].BrCC(=O)OC>>COC(COC1=C2C=C(N(C2=CC=C1)CC1=CC=CC2=CC=CC=C12)C)=O
Br[CH2:5][C:3]([O:2][CH3:1])=[O:4].[OH:6][c:7]1[cH:8][cH:9][cH:10][c:11]2[c:12]1[cH:13][c:14]([CH3:15])[n:16]2[CH2:17][c:18]1[cH:19][cH:20][cH:21][c:22]2[cH:23][cH:24][cH:25][cH:26][c:27]12>>[CH3:1][O:2][C:3](=[O:4])[CH2:5][O:6][c:7]1[cH:8][cH:9][cH:10][c:11]2[c:12]1[cH:13][c:14]([CH3:15])[n:16]2[CH2:17][c:18]1[cH:19][...
COC(=O)CBr.Cc1cc2c(O)cccc2n1Cc1cccc2ccccc12
COC(=O)COc1cccc2c1cc(C)n2Cc1cccc2ccccc12
null
null
null
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
50d675b335c583a6ce22e1164b27a78b18b9ca447d45137820c344bcb6369217
0865de4e1853c59ac25437e36fd18b03329566cb9eff4b4f0ce70d5714692fd3
c1ccc2c(Cn3ccc4ccccc43)cccc2c1
Br-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5].[#7;a:6]:[c:7]:[c:8]:[c:9](-[OH;D1;+0:10]):[c:11]>>[#7;a:6]:[c:7]:[c:8]:[c:9](-[O;H0;D2;+0:10]-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5]):[c:11]
463.7
[{"value": 45.0, "product": "COC(COC1=C2C=C(N(C2=CC=C1)CC1=CC=CC2=CC=CC=C12)C)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 463.7, "product": "COC(COC1=C2C=C(N(C2=CC=C1)CC1=CC=CC2=CC=CC=C12)C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using the procedure described in Example 1, Part E, 4-hydroxy-2-methyl-1-[(1-naphthalenyl)methyl]-1H-indole (796 mg, 2.8 mmol) was treated with 112 mg (2.8 mmol) of 60% NaH/mineral oil and then 0.27 mL (0.27 mmol) of methyl bromoacetate. The product was purified by chromatography over silica gel eluting with 20% EtOAc/...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester.Aromatic alcohol
Ester.Ether
null
null
c1cc2ccccc2[nH]1.c1ccc2ccccc2c1
HBr
null
null
null
COC(=O)CBr.Cc1cc2c(O)cccc2n1Cc1cccc2ccccc12>>COC(=O)COc1cccc2c1cc(C)n2Cc1cccc2ccccc12
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-b617f8b18b4f46baa67bd4b913fc8d21
CCC(=O)N(C)OC.COc1cccc(NC(=O)OC(C)(C)C)c1C>>CCC(=O)Cc1c(NC(=O)OC(C)(C)C)cccc1OC
C(C)(CC)[Li].C(C)(C)(C)OC(=O)NC1=C(C(=CC=C1)OC)C.CON(C(CC)=O)C>>C(C)(C)(C)OC(=O)NC1=C(C(=CC=C1)OC)CC(CC)=O
CON(C)[C:3]([CH2:2][CH3:1])=[O:4].[CH3:5][c:6]1[c:7]([NH:8][C:9](=[O:10])[O:11][C:12]([CH3:13])([CH3:14])[CH3:15])[cH:16][cH:17][cH:18][c:19]1[O:20][CH3:21]>>[CH3:1][CH2:2][C:3](=[O:4])[CH2:5][c:6]1[c:7]([NH:8][C:9](=[O:10])[O:11][C:12]([CH3:13])([CH3:14])[CH3:15])[cH:16][cH:17][cH:18][c:19]1[O:20][CH3:21]
CCC(=O)N(C)OC.COc1cccc(NC(=O)OC(C)(C)C)c1C
CCC(=O)Cc1c(NC(=O)OC(C)(C)C)cccc1OC
null
null
C1CCOC1.C1CCCCC1
C-C Coupling
OtherReaction
e4f529a3ae374940e7335150c613235054eca93a08615af33523f392ef733189
4113f0e803c7e6f9f731016c87e547bd597c0045514b87ca0ff3566df8b4b2c4
c1ccccc1
C-O-N(-C)-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[C;D1;H3:4].[CH3;D1;+0:5]-[c:6](:[c:7]):[c:8]>>[C;D1;H3:4]-[C:3]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[CH2;D2;+0:5]-[c:6](:[c:7]):[c:8]
null
[]
-60
CELSIUS
5
MINUTE
A solution of 140 mL (0.18 mol) of 1.3M sec-butyl lithium in cyclohexane was added slowly to N-tert-butoxycarbonyl-3-methoxy-2-methylaniline (21.3 g, 0.09 mol) in 250 mL of THF keeping the temperature below -40° C. with a dry ice-ethanol bath. The bath was removed and the temperature allowed to rise to 0° C. and then t...
10.6084/m9.figshare.5104873.v1
null
Tertiary amide
Ketone
null
null
c1ccccc1
HO-
C1CCOC1.C1CCCCC1
-60
0.083333
CCC(=O)N(C)OC.COc1cccc(NC(=O)OC(C)(C)C)c1C>C1CCOC1.C1CCCCC1>CCC(=O)Cc1c(NC(=O)OC(C)(C)C)cccc1OC
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-e34bd1862e53447ea8a43dbc7cad8a0e
BrCc1ccccc1.CCc1cc2c(OC)cccc2[nH]1>>CCc1cc2c(OC)cccc2n1Cc1ccccc1
C(C)C=1NC2=CC=CC(=C2C1)OC.[H-].[Na+].C(C1=CC=CC=C1)Br>>C(C)C=1N(C2=CC=CC(=C2C1)OC)CC1=CC=CC=C1
Br[CH2:14][c:15]1[cH:16][cH:17][cH:18][cH:19][cH:20]1.[CH3:1][CH2:2][c:3]1[cH:4][c:5]2[c:6]([O:7][CH3:8])[cH:9][cH:10][cH:11][c:12]2[nH:13]1>>[CH3:1][CH2:2][c:3]1[cH:4][c:5]2[c:6]([O:7][CH3:8])[cH:9][cH:10][cH:11][c:12]2[n:13]1[CH2:14][c:15]1[cH:16][cH:17][cH:18][cH:19][cH:20]1
BrCc1ccccc1.CCc1cc2c(OC)cccc2[nH]1
CCc1cc2c(OC)cccc2n1Cc1ccccc1
null
null
CN(C)C=O.O
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
16b46a8af20339f7ff0b611b4ac5dd01fe35ba577361e893c359dfa478dc1974
2e1e5fd9557b69cb528f6b2ffd179c67ef24ecb1a2c3994e1cdf0efe7ae19e9c
c1ccc(Cn2ccc3ccccc32)cc1
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[C:5]-[c:6]1:[c:7]:[c:8]:[c:9](:[c:10]):[nH;D2;+0:11]:1>>[C:5]-[c:6]1:[c:7]:[c:8]:[c:9](:[c:10]):[n;H0;D3;+0:11]:1-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4]
49
[{"value": 49.0, "product": "C(C)C=1N(C2=CC=CC(=C2C1)OC)CC1=CC=CC=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 48.7, "product": "C(C)C=1N(C2=CC=CC(=C2C1)OC)CC1=CC=CC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1.5
HOUR
2-Ethyl-4-methoxy-1H-indole (4.2 g, 24 mmol) was dissolved in 30 mL of DMF and 960 mg (24 mmol) of 60% NaH/mineral oil was added. After 1.5 hours, 2.9 mL (24 mmol) of benzyl bromide was added. After 4 hours, the mixture was diluted with water and extracted twice with ethyl acetate. The combined ethyl acetate was washed...
10.6084/m9.figshare.5104873.v1
null
Primary halide
null
c1ccc2[nH]ccc2c1
c1cc2ccccc2[nH]1
c1cc2ccccc2[nH]1.c1ccccc1
HBr
CN(C)C=O.O
null
1.5
BrCc1ccccc1.CCc1cc2c(OC)cccc2[nH]1>CN(C)C=O.O>CCc1cc2c(OC)cccc2n1Cc1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-a407b211fca84e1ca3a7311663e629e3
CCc1cc2c(OC)cccc2n1Cc1ccccc1>>CCc1cc2c(O)cccc2n1Cc1ccccc1
C(C)C=1N(C2=CC=CC(=C2C1)OC)CC1=CC=CC=C1.B(Br)(Br)Br.C(Cl)Cl>>C(C)C=1N(C2=CC=CC(=C2C1)O)CC1=CC=CC=C1
C[O:7][c:6]1[c:5]2[cH:4][c:3]([CH2:2][CH3:1])[n:12]([CH2:13][c:14]3[cH:15][cH:16][cH:17][cH:18][cH:19]3)[c:11]2[cH:10][cH:9][cH:8]1>>[CH3:1][CH2:2][c:3]1[cH:4][c:5]2[c:6]([OH:7])[cH:8][cH:9][cH:10][c:11]2[n:12]1[CH2:13][c:14]1[cH:15][cH:16][cH:17][cH:18][cH:19]1
CCc1cc2c(OC)cccc2n1Cc1ccccc1
CCc1cc2c(O)cccc2n1Cc1ccccc1
null
null
null
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc(Cn2ccc3ccccc32)cc1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]:[c:5]:[#7;a:6]>>[#7;a:6]:[c:5]:[c:4]:[c:2](-[OH;D1;+0:1]):[c:3]
54
[{"value": 54.0, "product": "C(C)C=1N(C2=CC=CC(=C2C1)O)CC1=CC=CC=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 53.7, "product": "C(C)C=1N(C2=CC=CC(=C2C1)O)CC1=CC=CC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
By the method used in Example 1, Part D, 3.1 g 11.7 mmol of 2ethyl-4-methoxy-1-(phenylmethyl)-1H-indole was O-demethylated by treating it with 48.6 mL of 1M BBr3 /CH2Cl2 to give a material that was chromatographed on silica gel (eluted with 20% EtOAc/hexane) to give 1.58 g (54% yield) of 2-ethyl-4-hydroxy-1-(phenylmeth...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1cc2ccccc2[nH]1.c1ccccc1
Other
null
null
null
CCc1cc2c(OC)cccc2n1Cc1ccccc1>>CCc1cc2c(O)cccc2n1Cc1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-093410cd99d04309ae041c581fea5247
CCc1cc2c(O)cccc2n1Cc1ccccc1.COC(=O)CBr>>CCc1cc2c(OCC(=O)OC)cccc2n1Cc1ccccc1
C(C)C=1N(C2=CC=CC(=C2C1)O)CC1=CC=CC=C1.[H-].[Na+].BrCC(=O)OC>>COC(COC1=C2C=C(N(C2=CC=C1)CC1=CC=CC=C1)CC)=O
[CH3:1][CH2:2][c:3]1[cH:4][c:5]2[c:6]([OH:7])[cH:13][cH:14][cH:15][c:16]2[n:17]1[CH2:18][c:19]1[cH:20][cH:21][cH:22][cH:23][cH:24]1.Br[CH2:8][C:9](=[O:10])[O:11][CH3:12]>>[CH3:1][CH2:2][c:3]1[cH:4][c:5]2[c:6]([O:7][CH2:8][C:9](=[O:10])[O:11][CH3:12])[cH:13][cH:14][cH:15][c:16]2[n:17]1[CH2:18][c:19]1[cH:20][cH:21][cH:22...
CCc1cc2c(O)cccc2n1Cc1ccccc1.COC(=O)CBr
CCc1cc2c(OCC(=O)OC)cccc2n1Cc1ccccc1
null
null
null
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
50d675b335c583a6ce22e1164b27a78b18b9ca447d45137820c344bcb6369217
0865de4e1853c59ac25437e36fd18b03329566cb9eff4b4f0ce70d5714692fd3
c1ccc(Cn2ccc3ccccc32)cc1
Br-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5].[#7;a:6]:[c:7]:[c:8]:[c:9](-[OH;D1;+0:10]):[c:11]>>[#7;a:6]:[c:7]:[c:8]:[c:9](-[O;H0;D2;+0:10]-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5]):[c:11]
69
[{"value": 69.0, "product": "COC(COC1=C2C=C(N(C2=CC=C1)CC1=CC=CC=C1)CC)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 68.3, "product": "COC(COC1=C2C=C(N(C2=CC=C1)CC1=CC=CC=C1)CC)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using the procedure described in Example 1, Part E, 2-ethyl-4-hydroxy-1-(phenylmethyl)-1H-indole (1.56 g, 6.2 mmol) was treated with 248 mg (6.2 mmol) of 60% NaH/mineral oil and then 0.6 mL (6.2 mmol) of methyl bromoacetate. The product was purified by chromatography over silica gel eluting with 20% EtOAc/hexane, to gi...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester.Aromatic alcohol
Ester.Ether
null
null
c1cc2ccccc2[nH]1.c1ccccc1
HBr
null
null
null
CCc1cc2c(O)cccc2n1Cc1ccccc1.COC(=O)CBr>>CCc1cc2c(OCC(=O)OC)cccc2n1Cc1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-4103d8fa652146e388cdb839eb898e60
CCc1cc2c(O)cccc2n1Cc1cccc(Cl)c1.COC(=O)CBr>>CCc1cc2c(OCC(=O)OC)cccc2n1Cc1cccc(Cl)c1
ClC=1C=C(C=CC1)CN1C(=CC2=C(C=CC=C12)O)CC.[H-].[Na+].BrCC(=O)OC>>COC(COC1=C2C=C(N(C2=CC=C1)CC1=CC(=CC=C1)Cl)CC)=O
[CH3:1][CH2:2][c:3]1[cH:4][c:5]2[c:6]([OH:7])[cH:13][cH:14][cH:15][c:16]2[n:17]1[CH2:18][c:19]1[cH:20][cH:21][cH:22][c:23]([Cl:24])[cH:25]1.Br[CH2:8][C:9](=[O:10])[O:11][CH3:12]>>[CH3:1][CH2:2][c:3]1[cH:4][c:5]2[c:6]([O:7][CH2:8][C:9](=[O:10])[O:11][CH3:12])[cH:13][cH:14][cH:15][c:16]2[n:17]1[CH2:18][c:19]1[cH:20][cH:2...
CCc1cc2c(O)cccc2n1Cc1cccc(Cl)c1.COC(=O)CBr
CCc1cc2c(OCC(=O)OC)cccc2n1Cc1cccc(Cl)c1
null
null
null
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
50d675b335c583a6ce22e1164b27a78b18b9ca447d45137820c344bcb6369217
0865de4e1853c59ac25437e36fd18b03329566cb9eff4b4f0ce70d5714692fd3
c1ccc(Cn2ccc3ccccc32)cc1
Br-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5].[#7;a:6]:[c:7]:[c:8]:[c:9](-[OH;D1;+0:10]):[c:11]>>[#7;a:6]:[c:7]:[c:8]:[c:9](-[O;H0;D2;+0:10]-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5]):[c:11]
65
[{"value": 65.0, "product": "COC(COC1=C2C=C(N(C2=CC=C1)CC1=CC(=CC=C1)Cl)CC)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 64.9, "product": "COC(COC1=C2C=C(N(C2=CC=C1)CC1=CC(=CC=C1)Cl)CC)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using the procedure described in Example 1, Part E, 1-[(3-chlorophenyl)methyl]-2-ethyl-4-hydroxy-1H-indole (512 mg, 1.8 mmol) was treated with 72 mg (1.8 mmol) of 60% NaH/mineral oil and then 0.17 mL (1.8 mmol) of methyl bromoacetate. The product was purified by chromatography over silica gel eluting with 20% EtOAc/hex...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester.Aromatic alcohol
Ester.Ether
null
null
c1cc2ccccc2[nH]1.c1ccccc1
HBr
null
null
null
CCc1cc2c(O)cccc2n1Cc1cccc(Cl)c1.COC(=O)CBr>>CCc1cc2c(OCC(=O)OC)cccc2n1Cc1cccc(Cl)c1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-0c7e8d43292048a8b5363fc3cec7be00
CCc1c(C(=O)C(N)=O)c2c(OCC(=O)OC)cccc2n1Cc1cccc(Cl)c1>>CCc1c(C(=O)C(N)=O)c2c(OCC(=O)O)cccc2n1Cc1cccc(Cl)c1
COC(COC1=C2C(=C(N(C2=CC=C1)CC1=CC(=CC=C1)Cl)CC)C(C(=O)N)=O)=O.CO.[Na]>>NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=CC(=CC=C1)Cl)CC)=O
C[O:16][C:14]([CH2:13][O:12][c:11]1[c:10]2[c:4]([C:5](=[O:6])[C:7]([NH2:8])=[O:9])[c:3]([CH2:2][CH3:1])[n:21]([CH2:22][c:23]3[cH:24][cH:25][cH:26][c:27]([Cl:28])[cH:29]3)[c:20]2[cH:19][cH:18][cH:17]1)=[O:15]>>[CH3:1][CH2:2][c:3]1[c:4]([C:5](=[O:6])[C:7]([NH2:8])=[O:9])[c:10]2[c:11]([O:12][CH2:13][C:14](=[O:15])[OH:16])...
CCc1c(C(=O)C(N)=O)c2c(OCC(=O)OC)cccc2n1Cc1cccc(Cl)c1
CCc1c(C(=O)C(N)=O)c2c(OCC(=O)O)cccc2n1Cc1cccc(Cl)c1
null
null
[OH-].[Na+]
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1ccc(Cn2ccc3ccccc32)cc1
C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
64.6
[{"value": 61.0, "product": "NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=CC(=CC=C1)Cl)CC)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 64.6, "product": "NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=CC(=CC=C1)Cl)CC)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using the procedure described in Example 2, Part E, 418 mg (1 mmol) of [[3-(2-amino-1,2-dioxoethyl)1-[(3-chlorophenyl)methyl]-2-ethyl-1H-indol-4-yl]oxy]acetic acid methyl ester was hydrolyzed in 5 mL of 1N NaOH and 15 mL of MeOH to give 268 mg (61% yield) of [[3-(2-amino-1,2-dioxoethyl)1-[(3-chlorophenyl)methyl]-2-ethy...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1cc2ccccc2[nH]1.c1ccccc1
Other
[OH-].[Na+]
null
null
CCc1c(C(=O)C(N)=O)c2c(OCC(=O)OC)cccc2n1Cc1cccc(Cl)c1>[OH-].[Na+]>CCc1c(C(=O)C(N)=O)c2c(OCC(=O)O)cccc2n1Cc1cccc(Cl)c1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-1b52bb60c1944a8bb041ea0a07e47ab6
CCc1cc2c(OC)cccc2n1Cc1ccccc1-c1ccccc1>>CCc1cc2c(O)cccc2n1Cc1ccccc1-c1ccccc1
C1(=C(C=CC=C1)CN1C(=CC2=C(C=CC=C12)OC)CC)C1=CC=CC=C1.ClCl>>C1(=C(C=CC=C1)CN1C(=CC2=C(C=CC=C12)O)CC)C1=CC=CC=C1
C[O:7][c:6]1[c:5]2[cH:4][c:3]([CH2:2][CH3:1])[n:12]([CH2:13][c:14]3[cH:15][cH:16][cH:17][cH:18][c:19]3-[c:20]3[cH:21][cH:22][cH:23][cH:24][cH:25]3)[c:11]2[cH:10][cH:9][cH:8]1>>[CH3:1][CH2:2][c:3]1[cH:4][c:5]2[c:6]([OH:7])[cH:8][cH:9][cH:10][c:11]2[n:12]1[CH2:13][c:14]1[cH:15][cH:16][cH:17][cH:18][c:19]1-[c:20]1[cH:21][...
CCc1cc2c(OC)cccc2n1Cc1ccccc1-c1ccccc1
CCc1cc2c(O)cccc2n1Cc1ccccc1-c1ccccc1
null
null
B(Br)(Br)Br
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc(-c2ccccc2Cn2ccc3ccccc32)cc1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]:[c:5]:[#7;a:6]>>[#7;a:6]:[c:5]:[c:4]:[c:2](-[OH;D1;+0:1]):[c:3]
69.3
[{"value": 69.0, "product": "C1(=C(C=CC=C1)CN1C(=CC2=C(C=CC=C12)O)CC)C1=CC=CC=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 69.3, "product": "C1(=C(C=CC=C1)CN1C(=CC2=C(C=CC=C12)O)CC)C1=CC=CC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
By the method used in Example 1, Part D, 911 mg (2.6 mmol) of 1-([1,1'-biphenyl]-2-ylmethyl)-2-ethyl-4-methoxy-1H-indole was O-demethylated by treating it with 10 mL of 1M BBr3 /CH2 Cl2. The crude product was chromatographed on silica gel and eluted with 20% EtOAc/hexane to give 590 mg (69% yield) of 1-([1,1'-biphenyl]...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1cc2ccccc2[nH]1.c1ccccc1.c1ccccc1
Other
B(Br)(Br)Br
null
null
CCc1cc2c(OC)cccc2n1Cc1ccccc1-c1ccccc1>B(Br)(Br)Br>CCc1cc2c(O)cccc2n1Cc1ccccc1-c1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-a877d6e90efd4757a0744545d7206df9
CCc1cc2c(O)cccc2n1Cc1ccccc1-c1ccccc1.COC(=O)CBr>>CCc1cc2c(OCC(=O)OC)cccc2n1Cc1ccccc1-c1ccccc1
C1(=C(C=CC=C1)CN1C(=CC2=C(C=CC=C12)O)CC)C1=CC=CC=C1.BrCC(=O)OC.[H-].[Na+]>>COC(COC1=C2C=C(N(C2=CC=C1)CC1=C(C=CC=C1)C1=CC=CC=C1)CC)=O
[CH3:1][CH2:2][c:3]1[cH:4][c:5]2[c:6]([OH:7])[cH:13][cH:14][cH:15][c:16]2[n:17]1[CH2:18][c:19]1[cH:20][cH:21][cH:22][cH:23][c:24]1-[c:25]1[cH:26][cH:27][cH:28][cH:29][cH:30]1.Br[CH2:8][C:9](=[O:10])[O:11][CH3:12]>>[CH3:1][CH2:2][c:3]1[cH:4][c:5]2[c:6]([O:7][CH2:8][C:9](=[O:10])[O:11][CH3:12])[cH:13][cH:14][cH:15][c:16]...
CCc1cc2c(O)cccc2n1Cc1ccccc1-c1ccccc1.COC(=O)CBr
CCc1cc2c(OCC(=O)OC)cccc2n1Cc1ccccc1-c1ccccc1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
50d675b335c583a6ce22e1164b27a78b18b9ca447d45137820c344bcb6369217
0865de4e1853c59ac25437e36fd18b03329566cb9eff4b4f0ce70d5714692fd3
c1ccc(-c2ccccc2Cn2ccc3ccccc32)cc1
Br-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5].[#7;a:6]:[c:7]:[c:8]:[c:9](-[OH;D1;+0:10]):[c:11]>>[#7;a:6]:[c:7]:[c:8]:[c:9](-[O;H0;D2;+0:10]-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5]):[c:11]
59
[{"value": 59.0, "product": "COC(COC1=C2C=C(N(C2=CC=C1)CC1=C(C=CC=C1)C1=CC=CC=C1)CC)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 58.6, "product": "COC(COC1=C2C=C(N(C2=CC=C1)CC1=C(C=CC=C1)C1=CC=CC=C1)CC)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
1-([1,1'-Biphenyl]-2-ylmethyl)-2-ethyl-4-hydroxy-1H-indole (911 mg, 2.8 mmol) was alkylated by treating with 0.26 mL (2.8 mmol) of methyl bromoacetate and 111 mg (2.8 mmol) of 60% NaH/mineral oil in DMF as described in Example 1, Part E. The product was purified by chromatography over silica gel eluting with 20% EtOAc/...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester.Aromatic alcohol
Ester.Ether
null
null
c1cc2ccccc2[nH]1.c1ccccc1.c1ccccc1
HBr
CN(C)C=O
null
null
CCc1cc2c(O)cccc2n1Cc1ccccc1-c1ccccc1.COC(=O)CBr>CN(C)C=O>CCc1cc2c(OCC(=O)OC)cccc2n1Cc1ccccc1-c1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-80e512c43b2e48fea09aa8564066a901
CCc1c(C(=O)C(N)=O)c2c(OCC(=O)OC)cccc2n1Cc1ccccc1-c1ccccc1>>CCc1c(C(=O)C(N)=O)c2c(OCC(=O)O)cccc2n1Cc1ccccc1-c1ccccc1
COC(COC1=C2C(=C(N(C2=CC=C1)CC1=C(C=CC=C1)C1=CC=CC=C1)CC)C(C(=O)N)=O)=O>>NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=C(C=CC=C1)C1=CC=CC=C1)CC)=O
C[O:16][C:14]([CH2:13][O:12][c:11]1[c:10]2[c:4]([C:5](=[O:6])[C:7]([NH2:8])=[O:9])[c:3]([CH2:2][CH3:1])[n:21]([CH2:22][c:23]3[cH:24][cH:25][cH:26][cH:27][c:28]3-[c:29]3[cH:30][cH:31][cH:32][cH:33][cH:34]3)[c:20]2[cH:19][cH:18][cH:17]1)=[O:15]>>[CH3:1][CH2:2][c:3]1[c:4]([C:5](=[O:6])[C:7]([NH2:8])=[O:9])[c:10]2[c:11]([O...
CCc1c(C(=O)C(N)=O)c2c(OCC(=O)OC)cccc2n1Cc1ccccc1-c1ccccc1
CCc1c(C(=O)C(N)=O)c2c(OCC(=O)O)cccc2n1Cc1ccccc1-c1ccccc1
null
null
[OH-].[Na+].CO
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1ccc(-c2ccccc2Cn2ccc3ccccc32)cc1
C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
59.3
[{"value": 59.0, "product": "NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=C(C=CC=C1)C1=CC=CC=C1)CC)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 59.3, "product": "NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=C(C=CC=C1)C1=CC=CC=C1)CC)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A mixture of 600 mg (1.3 mmol) of [[3-(2-amino-1,2-dioxoethyl)-1-([1,1'-biphenyl]-2-ylmethyl)-2-ethyl-1H-indol-4-yl]oxy]acetic acid methyl ester in 8 mL of 1N NaOH and 20 mL of MeOH was heated to maintain reflux for 0.67 hours, concentrated at reduced pressure and the residue taken up in EtOAc/water. The aqueous layer ...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1cc2ccccc2[nH]1.c1ccccc1.c1ccccc1
Other
[OH-].[Na+].CO
null
null
CCc1c(C(=O)C(N)=O)c2c(OCC(=O)OC)cccc2n1Cc1ccccc1-c1ccccc1>[OH-].[Na+].CO>CCc1c(C(=O)C(N)=O)c2c(OCC(=O)O)cccc2n1Cc1ccccc1-c1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-c14cbb85bdd54ffa9a54b464ff55f720
CCCC(=O)N(C)OC.COc1cccc(NC(=O)OC(C)(C)C)c1C>>CCCC(=O)Cc1c(NC(=O)OC(C)(C)C)cccc1OC
C(C)(CC)[Li].C(C)(C)(C)OC(=O)NC1=C(C(=CC=C1)OC)C.CON(C(CCC)=O)C.C1CCOC1.C1CCOC1>>C(C)(C)(C)OC(=O)NC1=C(C(=CC=C1)OC)CC(CCC)=O
CON(C)[C:4]([CH2:3][CH2:2][CH3:1])=[O:5].[CH3:6][c:7]1[c:8]([NH:9][C:10](=[O:11])[O:12][C:13]([CH3:14])([CH3:15])[CH3:16])[cH:17][cH:18][cH:19][c:20]1[O:21][CH3:22]>>[CH3:1][CH2:2][CH2:3][C:4](=[O:5])[CH2:6][c:7]1[c:8]([NH:9][C:10](=[O:11])[O:12][C:13]([CH3:14])([CH3:15])[CH3:16])[cH:17][cH:18][cH:19][c:20]1[O:21][CH3:...
CCCC(=O)N(C)OC.COc1cccc(NC(=O)OC(C)(C)C)c1C
CCCC(=O)Cc1c(NC(=O)OC(C)(C)C)cccc1OC
null
null
C1CCCCC1
C-C Coupling
OtherReaction
e4f529a3ae374940e7335150c613235054eca93a08615af33523f392ef733189
4113f0e803c7e6f9f731016c87e547bd597c0045514b87ca0ff3566df8b4b2c4
c1ccccc1
C-O-N(-C)-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[C:4].[CH3;D1;+0:5]-[c:6](:[c:7]):[c:8]>>[C:4]-[C:3]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[CH2;D2;+0:5]-[c:6](:[c:7]):[c:8]
null
[]
-60
CELSIUS
1
HOUR
A solution of 50 mL (65 mmol) of 1.3M sec-butyl lithium in cyclohexane was added slowly to N-tert-butoxycarbonyl-3-methoxy-2-methylaniline (7.7 g, 32.5 mmol) in 100 mL. of THF keeping the temperature below -40° C. with a dry ice-ethanol bath. The bath was removed and the temperature allowed to rise to -10° C. and then ...
10.6084/m9.figshare.5104873.v1
null
Tertiary amide
Ketone
null
null
c1ccccc1
HO-
C1CCCCC1
-60
1
CCCC(=O)N(C)OC.COc1cccc(NC(=O)OC(C)(C)C)c1C>C1CCCCC1>CCCC(=O)Cc1c(NC(=O)OC(C)(C)C)cccc1OC
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-a277cd76b49147da9acb93045c400b7a
CCCc1cc2c(OC)cccc2n1Cc1ccccc1-c1ccccc1>>CCCc1cc2c(O)cccc2n1Cc1ccccc1-c1ccccc1
C1(=C(C=CC=C1)CN1C(=CC2=C(C=CC=C12)OC)CCC)C1=CC=CC=C1.B(Br)(Br)Br.ClCl>>C1(=C(C=CC=C1)CN1C(=CC2=C(C=CC=C12)O)CCC)C1=CC=CC=C1
C[O:8][c:7]1[c:6]2[cH:5][c:4]([CH2:3][CH2:2][CH3:1])[n:13]([CH2:14][c:15]3[cH:16][cH:17][cH:18][cH:19][c:20]3-[c:21]3[cH:22][cH:23][cH:24][cH:25][cH:26]3)[c:12]2[cH:11][cH:10][cH:9]1>>[CH3:1][CH2:2][CH2:3][c:4]1[cH:5][c:6]2[c:7]([OH:8])[cH:9][cH:10][cH:11][c:12]2[n:13]1[CH2:14][c:15]1[cH:16][cH:17][cH:18][cH:19][c:20]1...
CCCc1cc2c(OC)cccc2n1Cc1ccccc1-c1ccccc1
CCCc1cc2c(O)cccc2n1Cc1ccccc1-c1ccccc1
null
null
null
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc(-c2ccccc2Cn2ccc3ccccc32)cc1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]:[c:5]:[#7;a:6]>>[#7;a:6]:[c:5]:[c:4]:[c:2](-[OH;D1;+0:1]):[c:3]
71.1
[{"value": 71.0, "product": "C1(=C(C=CC=C1)CN1C(=CC2=C(C=CC=C12)O)CCC)C1=CC=CC=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 71.1, "product": "C1(=C(C=CC=C1)CN1C(=CC2=C(C=CC=C12)O)CCC)C1=CC=CC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
By the method used in Example 1, Part D, 1.16 g (3.27 mmol) of 1-([1,1'-biphenyl]-2-ylmethyl)-4-methoxy-2-propyl-1H-indole was O-demethylated by treating it with 13 mL of 1M BBr3 /CH2 Cl2. The crude product was chromatographed on silica gel and eluted with 20% EtOAc/hexane to give 794 mg (71% yield) of 1-([1,1'-bipheny...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1cc2ccccc2[nH]1.c1ccccc1.c1ccccc1
Other
null
null
null
CCCc1cc2c(OC)cccc2n1Cc1ccccc1-c1ccccc1>>CCCc1cc2c(O)cccc2n1Cc1ccccc1-c1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-54c4d1b0dd394206b5c6af6828345e25
CCCc1cc2c(O)cccc2n1Cc1ccccc1-c1ccccc1.COC(=O)CBr>>CCCc1cc2c(OCC(=O)OC)cccc2n1Cc1ccccc1-c1ccccc1
C1(=C(C=CC=C1)CN1C(=CC2=C(C=CC=C12)O)CCC)C1=CC=CC=C1.BrCC(=O)OC.[H-].[Na+]>>COC(COC1=C2C=C(N(C2=CC=C1)CC1=C(C=CC=C1)C1=CC=CC=C1)CCC)=O
[CH3:1][CH2:2][CH2:3][c:4]1[cH:5][c:6]2[c:7]([OH:8])[cH:14][cH:15][cH:16][c:17]2[n:18]1[CH2:19][c:20]1[cH:21][cH:22][cH:23][cH:24][c:25]1-[c:26]1[cH:27][cH:28][cH:29][cH:30][cH:31]1.Br[CH2:9][C:10](=[O:11])[O:12][CH3:13]>>[CH3:1][CH2:2][CH2:3][c:4]1[cH:5][c:6]2[c:7]([O:8][CH2:9][C:10](=[O:11])[O:12][CH3:13])[cH:14][cH:...
CCCc1cc2c(O)cccc2n1Cc1ccccc1-c1ccccc1.COC(=O)CBr
CCCc1cc2c(OCC(=O)OC)cccc2n1Cc1ccccc1-c1ccccc1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
50d675b335c583a6ce22e1164b27a78b18b9ca447d45137820c344bcb6369217
0865de4e1853c59ac25437e36fd18b03329566cb9eff4b4f0ce70d5714692fd3
c1ccc(-c2ccccc2Cn2ccc3ccccc32)cc1
Br-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5].[#7;a:6]:[c:7]:[c:8]:[c:9](-[OH;D1;+0:10]):[c:11]>>[#7;a:6]:[c:7]:[c:8]:[c:9](-[O;H0;D2;+0:10]-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5]):[c:11]
56
[{"value": 56.0, "product": "COC(COC1=C2C=C(N(C2=CC=C1)CC1=C(C=CC=C1)C1=CC=CC=C1)CCC)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 56.0, "product": "COC(COC1=C2C=C(N(C2=CC=C1)CC1=C(C=CC=C1)C1=CC=CC=C1)CCC)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
1-([1,1'-Biphenyl]-2-ylmethyl)-4-hydroxy-2-propyl-1H-indole (794 mg, 2.8 mmol) was alkylated by treating with 0.22 mL (2.3 mmol) of methyl bromoacetate and 93 mg (2.3 mmol) of 60% NaH/mineral oil in DMF as described in Example 1, Part E. The product was purified by chromatography over silica gel eluting with 20% EtOAc/...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester.Aromatic alcohol
Ester.Ether
null
null
c1cc2ccccc2[nH]1.c1ccccc1.c1ccccc1
HBr
CN(C)C=O
null
null
CCCc1cc2c(O)cccc2n1Cc1ccccc1-c1ccccc1.COC(=O)CBr>CN(C)C=O>CCCc1cc2c(OCC(=O)OC)cccc2n1Cc1ccccc1-c1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-4a09a8e58b974e14b921d02856d38d2a
CCCc1c(C(=O)C(N)=O)c2c(OCC(=O)OC)cccc2n1Cc1ccccc1-c1ccccc1>>CCCc1c(C(=O)C(N)=O)c2c(OCC(=O)O)cccc2n1Cc1ccccc1-c1ccccc1
COC(COC1=C2C(=C(N(C2=CC=C1)CC1=C(C=CC=C1)C1=CC=CC=C1)CCC)C(C(=O)N)=O)=O>>NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=C(C=CC=C1)C1=CC=CC=C1)CCC)=O
C[O:17][C:15]([CH2:14][O:13][c:12]1[c:11]2[c:5]([C:6](=[O:7])[C:8]([NH2:9])=[O:10])[c:4]([CH2:3][CH2:2][CH3:1])[n:22]([CH2:23][c:24]3[cH:25][cH:26][cH:27][cH:28][c:29]3-[c:30]3[cH:31][cH:32][cH:33][cH:34][cH:35]3)[c:21]2[cH:20][cH:19][cH:18]1)=[O:16]>>[CH3:1][CH2:2][CH2:3][c:4]1[c:5]([C:6](=[O:7])[C:8]([NH2:9])=[O:10])...
CCCc1c(C(=O)C(N)=O)c2c(OCC(=O)OC)cccc2n1Cc1ccccc1-c1ccccc1
CCCc1c(C(=O)C(N)=O)c2c(OCC(=O)O)cccc2n1Cc1ccccc1-c1ccccc1
null
null
[OH-].[Na+].CO
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1ccc(-c2ccccc2Cn2ccc3ccccc32)cc1
C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
88.3
[{"value": 88.0, "product": "NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=C(C=CC=C1)C1=CC=CC=C1)CCC)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 88.3, "product": "NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=C(C=CC=C1)C1=CC=CC=C1)CCC)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
0.75
HOUR
A mixture of 440 mg (0.9 mmol) of [[3-(2-amino-1,2-dioxoethyl)-1-([1,1'-biphenyl]-2-ylmethyl)-2-propyl-1H-indol-4-yl]oxy]acetic acid methyl ester in 5 mL of 1N NaOH and 15 mL of MeOH was stirred for 0.75 hours, concentrated at reduced pressure and the residue taken up in EtOAc/water. The aqueous layer was separated, ma...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1cc2ccccc2[nH]1.c1ccccc1.c1ccccc1
Other
[OH-].[Na+].CO
null
0.75
CCCc1c(C(=O)C(N)=O)c2c(OCC(=O)OC)cccc2n1Cc1ccccc1-c1ccccc1>[OH-].[Na+].CO>CCCc1c(C(=O)C(N)=O)c2c(OCC(=O)O)cccc2n1Cc1ccccc1-c1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-34fde6f5003d4e6dab0c33bf86ba9d7f
COc1cccc(NC(=O)OC(C)(C)C)c1CC(=O)C1CC1>>CON(C)C(=O)C1CC1
C(C)(CC)[Li].C1(CC1)C(=O)CC1=C(C=CC=C1OC)NC(=O)OC(C)(C)C.C(C)(C)(C)OC(=O)NC1=C(C(=CC=C1)OC)C.C1CCOC1>>CON(C(=O)C1CC1)C
COc1cccc([NH:3]C(=O)OC(C)(C)C)c1C[C:5](=[O:6])[CH:7]1[CH2:8][CH2:9]1>>[CH3:1][O:2][N:3]([CH3:4])[C:5](=[O:6])[CH:7]1[CH2:8][CH2:9]1
COc1cccc(NC(=O)OC(C)(C)C)c1CC(=O)C1CC1
CON(C)C(=O)C1CC1
null
null
C1CCCCC1
Miscellaneous
OtherReaction
61d785c76a3ba47dcf3109c06bbe63e6f2eb472c023dbdf1e08fee621d950a07
367ca7a9199e8fe44c8c84b98b000d76432684a8ad9412335aad1964c6e1b04d
C1CC1
C-O-c1:c:c:c:c(-[NH;D2;+0:1]-C(=O)-O-C(-C)(-C)-C):c:1-C-[C;H0;D3;+0:2](=[O;D1;H0:3])-[C:4]1-[C:5]-[C:6]-1>>[C;D1;H3:7]-[#8:8]-[N;H0;D3;+0:1](-[C;D1;H3:9])-[C;H0;D3;+0:2](=[O;D1;H0:3])-[C:4]1-[C:5]-[C:6]-1
null
[]
null
null
null
null
Using the procedure described in Example 9, Part A, 100 mL (130 mmol) of 1.3M sec-butyl lithium in cyclohexane was reacted with N-tert-butoxycarbonyl-3-methoxy-2-methylaniline (15.4 g, 65 mmol) in 100 mL of THF and then with 8.4 g (65 mmol) of N-methoxy-N-methylcyclopropylcarboxamide to give crude [2-(tert-butoxycarbon...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ketone.Ether.Ether.Boc
Tertiary amide
c1ccccc1
null
C1CC1
HO-
C1CCCCC1
null
null
COc1cccc(NC(=O)OC(C)(C)C)c1CC(=O)C1CC1>C1CCCCC1>CON(C)C(=O)C1CC1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-90e6c368bccf4e26954b7d2f6022a3b3
COc1cccc2c1cc(C1CC1)n2Cc1ccccc1>>Oc1cccc2c1cc(C1CC1)n2Cc1ccccc1
C1(CC1)C=1N(C2=CC=CC(=C2C1)OC)CC1=CC=CC=C1.B(Br)(Br)Br.C(Cl)Cl>>C1(CC1)C=1N(C2=CC=CC(=C2C1)O)CC1=CC=CC=C1
C[O:1][c:2]1[cH:3][cH:4][cH:5][c:6]2[c:7]1[cH:8][c:9]([CH:10]1[CH2:11][CH2:12]1)[n:13]2[CH2:14][c:15]1[cH:16][cH:17][cH:18][cH:19][cH:20]1>>[OH:1][c:2]1[cH:3][cH:4][cH:5][c:6]2[c:7]1[cH:8][c:9]([CH:10]1[CH2:11][CH2:12]1)[n:13]2[CH2:14][c:15]1[cH:16][cH:17][cH:18][cH:19][cH:20]1
COc1cccc2c1cc(C1CC1)n2Cc1ccccc1
Oc1cccc2c1cc(C1CC1)n2Cc1ccccc1
null
null
null
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc(Cn2c(C3CC3)cc3ccccc32)cc1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]:[c:5]:[#7;a:6]>>[#7;a:6]:[c:5]:[c:4]:[c:2](-[OH;D1;+0:1]):[c:3]
52.2
[{"value": 52.0, "product": "C1(CC1)C=1N(C2=CC=CC(=C2C1)O)CC1=CC=CC=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 52.2, "product": "C1(CC1)C=1N(C2=CC=CC(=C2C1)O)CC1=CC=CC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
By the method used in Example 1, Part D, 630 g (2.3 mmol) of 2-cyclopropyl-4-methoxy-1-(phenylmethyl)-1H-indole was O-demethylated by treating it with 9 mL of 1M BBr3 /CH2Cl2. The crude product was chromatographed on silica gel and eluted with 20% EtOAc/hexane to give 316 mg (52% yield) of 2-cyclopropyl-4-hydroxy-1-(ph...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1cc2ccccc2[nH]1.C1CC1.c1ccccc1
Other
null
null
null
COc1cccc2c1cc(C1CC1)n2Cc1ccccc1>>Oc1cccc2c1cc(C1CC1)n2Cc1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-979ce933bd434af5ad518dda54297e9c
COC(=O)CBr.Oc1cccc2c1cc(C1CC1)n2Cc1ccccc1>>COC(=O)COc1cccc2c1cc(C1CC1)n2Cc1ccccc1
C1(CC1)C=1N(C2=CC=CC(=C2C1)O)CC1=CC=CC=C1.BrCC(=O)OC.[H-].[Na+]>>COC(COC1=C2C=C(N(C2=CC=C1)CC1=CC=CC=C1)C1CC1)=O
Br[CH2:5][C:3]([O:2][CH3:1])=[O:4].[OH:6][c:7]1[cH:8][cH:9][cH:10][c:11]2[c:12]1[cH:13][c:14]([CH:15]1[CH2:16][CH2:17]1)[n:18]2[CH2:19][c:20]1[cH:21][cH:22][cH:23][cH:24][cH:25]1>>[CH3:1][O:2][C:3](=[O:4])[CH2:5][O:6][c:7]1[cH:8][cH:9][cH:10][c:11]2[c:12]1[cH:13][c:14]([CH:15]1[CH2:16][CH2:17]1)[n:18]2[CH2:19][c:20]1[c...
COC(=O)CBr.Oc1cccc2c1cc(C1CC1)n2Cc1ccccc1
COC(=O)COc1cccc2c1cc(C1CC1)n2Cc1ccccc1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
50d675b335c583a6ce22e1164b27a78b18b9ca447d45137820c344bcb6369217
0865de4e1853c59ac25437e36fd18b03329566cb9eff4b4f0ce70d5714692fd3
c1ccc(Cn2c(C3CC3)cc3ccccc32)cc1
Br-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5].[#7;a:6]:[c:7]:[c:8]:[c:9](-[OH;D1;+0:10]):[c:11]>>[#7;a:6]:[c:7]:[c:8]:[c:9](-[O;H0;D2;+0:10]-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5]):[c:11]
63
[{"value": 63.0, "product": "COC(COC1=C2C=C(N(C2=CC=C1)CC1=CC=CC=C1)C1CC1)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 62.9, "product": "COC(COC1=C2C=C(N(C2=CC=C1)CC1=CC=CC=C1)C1CC1)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
2-Cyclopropyl-4-hydroxy-1-(phenylmethyl)-1H-indole (316 mg, 1.2 mmol) was alkylated by treating with 0.11 mL (1.2 mmol) of methyl bromoacetate and 48 mg (1.2 mmol) of 60% NaH/mineral oil in DMF as described in Example 1, Part E. The product was purified by chromatography over silica gel eluting with 20% EtOAc/hexane, t...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester.Aromatic alcohol
Ester.Ether
null
null
c1cc2ccccc2[nH]1.C1CC1.c1ccccc1
HBr
CN(C)C=O
null
null
COC(=O)CBr.Oc1cccc2c1cc(C1CC1)n2Cc1ccccc1>CN(C)C=O>COC(=O)COc1cccc2c1cc(C1CC1)n2Cc1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-9ed6f8ff991a4fce822b81a34a0e86c5
COC(=O)COc1cccc2c1c(C(=O)C(N)=O)c(C1CC1)n2Cc1ccccc1>>NC(=O)C(=O)c1c(C2CC2)n(Cc2ccccc2)c2cccc(OCC(=O)O)c12
COC(COC1=C2C(=C(N(C2=CC=C1)CC1=CC=CC=C1)C1CC1)C(C(=O)N)=O)=O>>NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=CC=CC=C1)C1CC1)=O
C[O:28][C:26]([CH2:25][O:24][c:23]1[cH:22][cH:21][cH:20][c:19]2[n:11]([CH2:12][c:13]3[cH:14][cH:15][cH:16][cH:17][cH:18]3)[c:7]([CH:8]3[CH2:9][CH2:10]3)[c:6]([C:4]([C:2]([NH2:1])=[O:3])=[O:5])[c:29]21)=[O:27]>>[NH2:1][C:2](=[O:3])[C:4](=[O:5])[c:6]1[c:7]([CH:8]2[CH2:9][CH2:10]2)[n:11]([CH2:12][c:13]2[cH:14][cH:15][cH:1...
COC(=O)COc1cccc2c1c(C(=O)C(N)=O)c(C1CC1)n2Cc1ccccc1
NC(=O)C(=O)c1c(C2CC2)n(Cc2ccccc2)c2cccc(OCC(=O)O)c12
null
null
[OH-].[Na+].CO
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1ccc(Cn2c(C3CC3)cc3ccccc32)cc1
C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
80
[{"value": 80.0, "product": "NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=CC=CC=C1)C1CC1)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 79.8, "product": "NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=CC=CC=C1)C1CC1)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A mixture of 220 mg (0.54 mmol) of [[3-(2-amino-1,2-dioxoethyl)-2-cyclopropyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid methyl ester in 5 mL of 1N NaOH and 15 mL of MeOH was heated to maintain reflux for 0.67 hours, concentrated at reduced pressure and the residue taken up in EtOAc/water. The aqueous layer was sep...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
C1CC1.c1ccccc1.c1cc2ccccc2[nH]1
Other
[OH-].[Na+].CO
null
null
COC(=O)COc1cccc2c1c(C(=O)C(N)=O)c(C1CC1)n2Cc1ccccc1>[OH-].[Na+].CO>NC(=O)C(=O)c1c(C2CC2)n(Cc2ccccc2)c2cccc(OCC(=O)O)c12
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-4a94e879ce5b4777a46e8ccc576b08e1
COc1cccc2c1cc(C1CC1)n2Cc1ccccc1-c1ccccc1>>Oc1cccc2c1cc(C1CC1)n2Cc1ccccc1-c1ccccc1
C1(=C(C=CC=C1)CN1C(=CC2=C(C=CC=C12)OC)C1CC1)C1=CC=CC=C1.B(Br)(Br)Br.ClCl>>C1(=C(C=CC=C1)CN1C(=CC2=C(C=CC=C12)O)C1CC1)C1=CC=CC=C1
C[O:1][c:2]1[cH:3][cH:4][cH:5][c:6]2[c:7]1[cH:8][c:9]([CH:10]1[CH2:11][CH2:12]1)[n:13]2[CH2:14][c:15]1[cH:16][cH:17][cH:18][cH:19][c:20]1-[c:21]1[cH:22][cH:23][cH:24][cH:25][cH:26]1>>[OH:1][c:2]1[cH:3][cH:4][cH:5][c:6]2[c:7]1[cH:8][c:9]([CH:10]1[CH2:11][CH2:12]1)[n:13]2[CH2:14][c:15]1[cH:16][cH:17][cH:18][cH:19][c:20]1...
COc1cccc2c1cc(C1CC1)n2Cc1ccccc1-c1ccccc1
Oc1cccc2c1cc(C1CC1)n2Cc1ccccc1-c1ccccc1
null
null
null
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc(-c2ccccc2Cn2c(C3CC3)cc3ccccc32)cc1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]:[c:5]:[#7;a:6]>>[#7;a:6]:[c:5]:[c:4]:[c:2](-[OH;D1;+0:1]):[c:3]
29.2
[{"value": 29.0, "product": "C1(=C(C=CC=C1)CN1C(=CC2=C(C=CC=C12)O)C1CC1)C1=CC=CC=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 29.2, "product": "C1(=C(C=CC=C1)CN1C(=CC2=C(C=CC=C12)O)C1CC1)C1=CC=CC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
By the method used in Example 1, Part D, 1.25 g (3.7 mmol) of 1-([1,1'-biphenyl]-2-ylmethyl)-2-cyclopropyl-4-methoxyl-1H-indole was O-demethylated by treating it with 15 mL of 1M BBr3 /CH2 Cl2. The crude product was chromatographed on silica gel and eluted with 20% EtOAc/hexane to give 367 mg (29% yield) of 1-([1,1'-bi...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1cc2ccccc2[nH]1.C1CC1.c1ccccc1.c1ccccc1
Other
null
null
null
COc1cccc2c1cc(C1CC1)n2Cc1ccccc1-c1ccccc1>>Oc1cccc2c1cc(C1CC1)n2Cc1ccccc1-c1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-541c15dabcdf432da126da56fb2ac26d
COC(=O)CBr.Oc1cccc2c1cc(C1CC1)n2Cc1ccccc1-c1ccccc1>>COC(=O)COc1cccc2c1cc(C1CC1)n2Cc1ccccc1-c1ccccc1
C1(=C(C=CC=C1)CN1C(=CC2=C(C=CC=C12)O)C1CC1)C1=CC=CC=C1.BrCC(=O)OC.[H-].[Na+]>>COC(COC1=C2C=C(N(C2=CC=C1)CC1=C(C=CC=C1)C1=CC=CC=C1)C1CC1)=O
Br[CH2:5][C:3]([O:2][CH3:1])=[O:4].[OH:6][c:7]1[cH:8][cH:9][cH:10][c:11]2[c:12]1[cH:13][c:14]([CH:15]1[CH2:16][CH2:17]1)[n:18]2[CH2:19][c:20]1[cH:21][cH:22][cH:23][cH:24][c:25]1-[c:26]1[cH:27][cH:28][cH:29][cH:30][cH:31]1>>[CH3:1][O:2][C:3](=[O:4])[CH2:5][O:6][c:7]1[cH:8][cH:9][cH:10][c:11]2[c:12]1[cH:13][c:14]([CH:15]...
COC(=O)CBr.Oc1cccc2c1cc(C1CC1)n2Cc1ccccc1-c1ccccc1
COC(=O)COc1cccc2c1cc(C1CC1)n2Cc1ccccc1-c1ccccc1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
50d675b335c583a6ce22e1164b27a78b18b9ca447d45137820c344bcb6369217
0865de4e1853c59ac25437e36fd18b03329566cb9eff4b4f0ce70d5714692fd3
c1ccc(-c2ccccc2Cn2c(C3CC3)cc3ccccc32)cc1
Br-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5].[#7;a:6]:[c:7]:[c:8]:[c:9](-[OH;D1;+0:10]):[c:11]>>[#7;a:6]:[c:7]:[c:8]:[c:9](-[O;H0;D2;+0:10]-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5]):[c:11]
59
[{"value": 59.0, "product": "COC(COC1=C2C=C(N(C2=CC=C1)CC1=C(C=CC=C1)C1=CC=CC=C1)C1CC1)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 58.5, "product": "COC(COC1=C2C=C(N(C2=CC=C1)CC1=C(C=CC=C1)C1=CC=CC=C1)C1CC1)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
1-([1,1'-Biphenyl]-2-ylmethyl)-2-cyclopropyl-4-hydroxy-1H-indole (367 mg, 1.1 mmol) was alkylated by treating with 0.1 mL (1.1 mmol) of methyl bromoacetate and 43 mg (1.1 mmol) of 60% NaH/mineral oil in DMF as described in Example 1, Part E. The product was purified by chromatography over silica gel eluting with 20% Et...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester.Aromatic alcohol
Ester.Ether
null
null
c1cc2ccccc2[nH]1.C1CC1.c1ccccc1.c1ccccc1
HBr
CN(C)C=O
null
null
COC(=O)CBr.Oc1cccc2c1cc(C1CC1)n2Cc1ccccc1-c1ccccc1>CN(C)C=O>COC(=O)COc1cccc2c1cc(C1CC1)n2Cc1ccccc1-c1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-f3720dc9407a4917ba4d4d639555e0d7
COC(=O)COc1cccc2c1c(C(=O)C(N)=O)c(C1CC1)n2Cc1ccccc1-c1ccccc1>>NC(=O)C(=O)c1c(C2CC2)n(Cc2ccccc2-c2ccccc2)c2cccc(OCC(=O)O)c12
COC(COC1=C2C(=C(N(C2=CC=C1)CC1=C(C=CC=C1)C1=CC=CC=C1)C1CC1)C(C(=O)N)=O)=O>>NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=C(C=CC=C1)C1=CC=CC=C1)C1CC1)=O
C[O:34][C:32]([CH2:31][O:30][c:29]1[cH:28][cH:27][cH:26][c:25]2[n:11]([CH2:12][c:13]3[cH:14][cH:15][cH:16][cH:17][c:18]3-[c:19]3[cH:20][cH:21][cH:22][cH:23][cH:24]3)[c:7]([CH:8]3[CH2:9][CH2:10]3)[c:6]([C:4]([C:2]([NH2:1])=[O:3])=[O:5])[c:35]21)=[O:33]>>[NH2:1][C:2](=[O:3])[C:4](=[O:5])[c:6]1[c:7]([CH:8]2[CH2:9][CH2:10]...
COC(=O)COc1cccc2c1c(C(=O)C(N)=O)c(C1CC1)n2Cc1ccccc1-c1ccccc1
NC(=O)C(=O)c1c(C2CC2)n(Cc2ccccc2-c2ccccc2)c2cccc(OCC(=O)O)c12
null
null
[OH-].[Na+].CO
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1ccc(-c2ccccc2Cn2c(C3CC3)cc3ccccc32)cc1
C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
62.3
[{"value": 62.0, "product": "NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=C(C=CC=C1)C1=CC=CC=C1)C1CC1)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 62.3, "product": "NC(C(=O)C1=C(N(C2=CC=CC(=C12)OCC(=O)O)CC1=C(C=CC=C1)C1=CC=CC=C1)C1CC1)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
0.5
HOUR
A mixture of 175 mg (0.36 mmol) of [[3-(2-amino-1,2-dioxoethyl)-1-([1,1'-biphenyl]-2-ylmethyl)-2-cyclopropyl-1H-indol-4-yl]0xy]acetic acid methyl ester in 4 mL of 1N NaOH and 10 mL of MeOH was stirred for 0.5 hours, concentrated at reduced pressure and the residue taken up in EtOAc/water. The aqueous layer was separate...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
C1CC1.c1ccccc1.c1ccccc1.c1cc2ccccc2[nH]1
Other
[OH-].[Na+].CO
null
0.5
COC(=O)COc1cccc2c1c(C(=O)C(N)=O)c(C1CC1)n2Cc1ccccc1-c1ccccc1>[OH-].[Na+].CO>NC(=O)C(=O)c1c(C2CC2)n(Cc2ccccc2-c2ccccc2)c2cccc(OCC(=O)O)c12
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-e69aac2b440d40a899e0f8fb35b22bdc
CCC(=O)N(C)OC.COc1ccc(NC(=O)OC(C)(C)C)c(C)c1>>CCC(=O)Cc1cc(OC)ccc1NC(=O)OC(C)(C)C
CON(C(CC)=O)C.C(C)(CC)[Li].C1CCCCC1.C(C)(C)(C)OC(=O)NC1=C(C=C(C=C1)OC)C>>C(C)(C)(C)OC(=O)NC1=C(C=C(C=C1)OC)CC(CC)=O
CON(C)[C:3]([CH2:2][CH3:1])=[O:4].[CH3:5][c:6]1[cH:7][c:8]([O:9][CH3:10])[cH:11][cH:12][c:13]1[NH:14][C:15](=[O:16])[O:17][C:18]([CH3:19])([CH3:20])[CH3:21]>>[CH3:1][CH2:2][C:3](=[O:4])[CH2:5][c:6]1[cH:7][c:8]([O:9][CH3:10])[cH:11][cH:12][c:13]1[NH:14][C:15](=[O:16])[O:17][C:18]([CH3:19])([CH3:20])[CH3:21]
CCC(=O)N(C)OC.COc1ccc(NC(=O)OC(C)(C)C)c(C)c1
CCC(=O)Cc1cc(OC)ccc1NC(=O)OC(C)(C)C
null
null
C1CCOC1
C-C Coupling
OtherReaction
e4f529a3ae374940e7335150c613235054eca93a08615af33523f392ef733189
4113f0e803c7e6f9f731016c87e547bd597c0045514b87ca0ff3566df8b4b2c4
c1ccccc1
C-O-N(-C)-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[C;D1;H3:4].[CH3;D1;+0:5]-[c:6](:[c:7]):[c:8]>>[C;D1;H3:4]-[C:3]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[CH2;D2;+0:5]-[c:6](:[c:7]):[c:8]
74.3
[{"value": 74.0, "product": "C(C)(C)(C)OC(=O)NC1=C(C=C(C=C1)OC)CC(CC)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 74.3, "product": "C(C)(C)(C)OC(=O)NC1=C(C=C(C=C1)OC)CC(CC)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
-60
CELSIUS
1
HOUR
A solution of 1.3M sec-butyl lithium/cyclohexane (81 mL, 0.105 mol) was added slowly to 11.85 g (0.05 mol) of N-tert-butoxycarbonyl-4-methoxy-2-methylaniline in 80 mL of THF while keeping the temperature below -40° C. with a dry ice-ethanol bath. The bath was removed and the temperature allowed to rise to -20° C. and t...
10.6084/m9.figshare.5104873.v1
null
Tertiary amide
Ketone
null
null
c1ccccc1
HO-
C1CCOC1
-60
1
CCC(=O)N(C)OC.COc1ccc(NC(=O)OC(C)(C)C)c(C)c1>C1CCOC1>CCC(=O)Cc1cc(OC)ccc1NC(=O)OC(C)(C)C
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-a1ba7dd968ef42de8f7d8852721b5d4d
CCC(=O)Cc1cc(OC)ccc1NC(=O)OC(C)(C)C>>CCc1cc2cc(OC)ccc2[nH]1
C(C)(C)(C)OC(=O)NC1=C(C=C(C=C1)OC)CC(CC)=O>>C(C)C=1NC2=CC=C(C=C2C1)OC
CC(C)(C)OC(=O)[NH:13][c:12]1[c:5]([CH2:4][C:3](=O)[CH2:2][CH3:1])[cH:6][c:7]([O:8][CH3:9])[cH:10][cH:11]1>>[CH3:1][CH2:2][c:3]1[cH:4][c:5]2[cH:6][c:7]([O:8][CH3:9])[cH:10][cH:11][c:12]2[nH:13]1
CCC(=O)Cc1cc(OC)ccc1NC(=O)OC(C)(C)C
CCc1cc2cc(OC)ccc2[nH]1
null
null
C(Cl)Cl.FC(C(=O)O)(F)F
Aromatic Heterocycle Formation
OtherReaction
4256a7d4346290a91222b072361f174c5a38107f7ea1eee59c70bf31e7b48d79
77f05d7356e9f98235278e7a1d7d92c710704d628109c2563233a98cb56f0099
c1ccc2[nH]ccc2c1
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[c:2](:[c:3]):[c:4](-[CH2;D2;+0:5]-[C;H0;D3;+0:6](=O)-[C:7]-[C;D1;H3:8]):[c:9]>>[C;D1;H3:8]-[C:7]-[c;H0;D3;+0:6]1:[cH;D2;+0:5]:[c:4](:[c:9]):[c:2](:[c:3]):[nH;D2;+0:1]:1
58
[{"value": 58.0, "product": "C(C)C=1NC2=CC=C(C=C2C1)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 58.0, "product": "C(C)C=1NC2=CC=C(C=C2C1)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
1-[2-(tert-Butoxycarbonylamino)-5-methoxyphenyl]-2-butanone (7.33 g, 0.025 mol) in 120 mL of CH2Cl2 and 20 mL of trifluoroacetic acid was stirred for 20 hours, washed with water, NaHCO3 solution and the product chromatographed on silica (eluted with 20% EtOAc/hexane) to give 2.54 g (58% yield) of 2-ethyl-5-methoxy-1H-i...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ketone.Ether.Boc
null
c1ccccc1
c1ccc2[nH]ccc2c1
c1ccc2[nH]ccc2c1
HO-
C(Cl)Cl.FC(C(=O)O)(F)F
null
null
CCC(=O)Cc1cc(OC)ccc1NC(=O)OC(C)(C)C>C(Cl)Cl.FC(C(=O)O)(F)F>CCc1cc2cc(OC)ccc2[nH]1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-58e3159b6ca6432dae5a788f94e6f3a6
BrCc1ccccc1.CCc1cc2cc(OC)ccc2[nH]1>>CCc1cc2cc(OC)ccc2n1Cc1ccccc1
C(C1=CC=CC=C1)Br.C1CCOC1.[H-].[Na+].C(C)C=1NC2=CC=C(C=C2C1)OC>>C(C)C=1N(C2=CC=C(C=C2C1)OC)CC1=CC=CC=C1
Br[CH2:14][c:15]1[cH:16][cH:17][cH:18][cH:19][cH:20]1.[CH3:1][CH2:2][c:3]1[cH:4][c:5]2[cH:6][c:7]([O:8][CH3:9])[cH:10][cH:11][c:12]2[nH:13]1>>[CH3:1][CH2:2][c:3]1[cH:4][c:5]2[cH:6][c:7]([O:8][CH3:9])[cH:10][cH:11][c:12]2[n:13]1[CH2:14][c:15]1[cH:16][cH:17][cH:18][cH:19][cH:20]1
BrCc1ccccc1.CCc1cc2cc(OC)ccc2[nH]1
CCc1cc2cc(OC)ccc2n1Cc1ccccc1
null
null
CN(C)C=O.O
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
92cc004fc3e2a92f5c9aa0385cdf93f1126e35d5aa485f4f5fe9240c9543c8fe
2e1e5fd9557b69cb528f6b2ffd179c67ef24ecb1a2c3994e1cdf0efe7ae19e9c
c1ccc(Cn2ccc3ccccc32)cc1
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[C:5]-[c:6]1:[c:7]:[c:8]:[c:9](:[c:10]):[nH;D2;+0:11]:1>>[C:5]-[c:6]1:[c:7]:[c:8]:[c:9](:[c:10]):[n;H0;D3;+0:11]:1-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4]
82
[{"value": 82.0, "product": "C(C)C=1N(C2=CC=C(C=C2C1)OC)CC1=CC=CC=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 80.6, "product": "C(C)C=1N(C2=CC=C(C=C2C1)OC)CC1=CC=CC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
0.17
HOUR
2-Ethyl-5-methoxy-1H-indole (5.6 g, 21.5 mmol) was dissolved in 150 mL of DMF and 20 mL of THF and 1.0 g (25 mmol) of 60% sodium hydride was added. After stirring for 0.17 hours, 3.0 mL (25 mmol) of benzyl bromide was added. The mixture was stirred at room temperature for 10 hours, diluted with water and extracted with...
10.6084/m9.figshare.5104873.v1
null
Primary halide
null
c1ccc2[nH]ccc2c1
c1ccc2[nH]ccc2c1
c1ccc2[nH]ccc2c1.c1ccccc1
HBr
CN(C)C=O.O
null
0.17
BrCc1ccccc1.CCc1cc2cc(OC)ccc2[nH]1>CN(C)C=O.O>CCc1cc2cc(OC)ccc2n1Cc1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-799c09d15d7344de8182a414b9bb0211
CCc1c(C(=O)C(N)=O)c2cc(OCCCC(=O)OC(C)(C)C)ccc2n1Cc1ccccc1>>CCc1c(C(=O)C(N)=O)c2cc(OCCCC(=O)O)ccc2n1Cc1ccccc1
C(C)(C)(C)OC(CCCOC=1C=C2C(=C(N(C2=CC1)CC1=CC=CC=C1)CC)C(C(=O)N)=O)=O>>NC(C(=O)C1=C(N(C2=CC=C(C=C12)OCCCC(=O)O)CC1=CC=CC=C1)CC)=O
CC(C)(C)[O:19][C:17]([CH2:16][CH2:15][CH2:14][O:13][c:12]1[cH:11][c:10]2[c:4]([C:5](=[O:6])[C:7]([NH2:8])=[O:9])[c:3]([CH2:2][CH3:1])[n:23]([CH2:24][c:25]3[cH:26][cH:27][cH:28][cH:29][cH:30]3)[c:22]2[cH:21][cH:20]1)=[O:18]>>[CH3:1][CH2:2][c:3]1[c:4]([C:5](=[O:6])[C:7]([NH2:8])=[O:9])[c:10]2[cH:11][c:12]([O:13][CH2:14][...
CCc1c(C(=O)C(N)=O)c2cc(OCCCC(=O)OC(C)(C)C)ccc2n1Cc1ccccc1
CCc1c(C(=O)C(N)=O)c2cc(OCCCC(=O)O)ccc2n1Cc1ccccc1
null
null
C(Cl)Cl.FC(C(=O)O)(F)F
Deprotection
Deprotection of carboxylic acid
152e5537e48c95b4a3e767536b0f9f68d1308e5f484070828ab5ed951805157a
7f019d4cfe9b3036d0a2d3a3209aa0e1fcb05418ebee15a4be5e125d315d5f01
c1ccc(Cn2ccc3ccccc32)cc1
C-C(-C)(-C)-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
63.1
[{"value": 63.0, "product": "NC(C(=O)C1=C(N(C2=CC=C(C=C12)OCCCC(=O)O)CC1=CC=CC=C1)CC)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 63.1, "product": "NC(C(=O)C1=C(N(C2=CC=C(C=C12)OCCCC(=O)O)CC1=CC=CC=C1)CC)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 450 mg (0.97 mmol) of 4-[[3-(2-amino-1,2-dioxoethyl)-2-ethyl-1-(phenylmethyl)-1H-indol-5-yl]oxy]butanoic acid tert-butyl ester in 75 mL of methylene chloride and 1 mL of trifluoroacetic acid was stirred-at room temperature for 2.25 hours and concentrated at reduced pressure. The residue was chromatographe...
10.6084/m9.figshare.5104873.v1
null
Ester.Boc
Carboxylic acid
null
null
c1ccc2[nH]ccc2c1.c1ccccc1
Other
C(Cl)Cl.FC(C(=O)O)(F)F
null
null
CCc1c(C(=O)C(N)=O)c2cc(OCCCC(=O)OC(C)(C)C)ccc2n1Cc1ccccc1>C(Cl)Cl.FC(C(=O)O)(F)F>CCc1c(C(=O)C(N)=O)c2cc(OCCCC(=O)O)ccc2n1Cc1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-39e0ce5ac6fe453c825a8e16562f634e
BrCc1ccccc1.COc1ccc2[nH]ccc2c1>>Oc1ccc2c(ccn2Cc2ccccc2)c1
B(Br)(Br)Br.C(Cl)Cl.COC=1C=C2C=CNC2=CC1.[H-].[Na+].C(C1=CC=CC=C1)Br>>OC=1C=C2C=CN(C2=CC1)CC1=CC=CC=C1
Br[CH2:10][c:11]1[cH:12][cH:13][cH:14][cH:15][cH:16]1.C[O:1][c:2]1[cH:3][cH:4][c:5]2[c:6]([cH:7][cH:8][nH:9]2)[cH:17]1>>[OH:1][c:2]1[cH:3][cH:4][c:5]2[c:6]([cH:7][cH:8][n:9]2[CH2:10][c:11]2[cH:12][cH:13][cH:14][cH:15][cH:16]2)[cH:17]1
BrCc1ccccc1.COc1ccc2[nH]ccc2c1
Oc1ccc2c(ccn2Cc2ccccc2)c1
null
null
C(Cl)Cl
Heteroatom Alkylation and Arylation
OtherReaction
b8b8c936f1222ba4dcc39cac77417eb1c24a0b1a19b1a7aa4ee3960753f3d06a
cf1086715641611cede41736f13bebea69e2422e9980e019e3ae4f0472190f48
c1ccc(Cn2ccc3ccccc32)cc1
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].C-[O;H0;D2;+0:5]-[c:6]1:[c:7]:[c:8]2:[c:9]:[c:10]:[nH;D2;+0:11]:[c:12]:2:[c:13]:[c:14]:1>>[OH;D1;+0:5]-[c:6]1:[c:7]:[c:8]2:[c:9]:[c:10]:[n;H0;D3;+0:11](-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4]):[c:12]:2:[c:13]:[c:14]:1
19
[{"value": 19.0, "product": "OC=1C=C2C=CN(C2=CC1)CC1=CC=CC=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 18.1, "product": "OC=1C=C2C=CN(C2=CC1)CC1=CC=CC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
-5
CELSIUS
1.75
HOUR
5-Methoxy-1H-indole (5.6 g, 21.5 mmol) was reacted with 1.0 g (25 mmol) of 60% sodium hydride and then 3.0 mL (25 mmol) of benzyl bromide by the method described in Example 12, Part D to give crude 5-methoxy-1-(phenylmethyl)-1H-indole. This material was dissolved in 250 mL of methylene chloride, cooled to -5° C., 50 mL...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ether
Aromatic alcohol
c1ccc2[nH]ccc2c1
c1ccc2[nH]ccc2c1
c1ccc2[nH]ccc2c1.c1ccccc1
HBr
C(Cl)Cl
-5
1.75
BrCc1ccccc1.COc1ccc2[nH]ccc2c1>C(Cl)Cl>Oc1ccc2c(ccn2Cc2ccccc2)c1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-bbf8230acb4c4efbbe2e5b95721c489b
BrCc1ccccc1.CCc1cc2c([N+](=O)[O-])cccc2[nH]1>>CCc1cc2c([N+](=O)[O-])cccc2n1Cc1ccccc1
C(C1=CC=CC=C1)Br.C(C)C=1NC2=CC=CC(=C2C1)[N+](=O)[O-].[H-].[Na+].CCCCCC>>C1(=CC=CC=C1)CN1C(=CC2=C(C=CC=C12)[N+](=O)[O-])CC
Br[CH2:15][c:16]1[cH:17][cH:18][cH:19][cH:20][cH:21]1.[CH3:1][CH2:2][c:3]1[cH:4][c:5]2[c:6]([N+:7](=[O:8])[O-:9])[cH:10][cH:11][cH:12][c:13]2[nH:14]1>>[CH3:1][CH2:2][c:3]1[cH:4][c:5]2[c:6]([N+:7](=[O:8])[O-:9])[cH:10][cH:11][cH:12][c:13]2[n:14]1[CH2:15][c:16]1[cH:17][cH:18][cH:19][cH:20][cH:21]1
BrCc1ccccc1.CCc1cc2c([N+](=O)[O-])cccc2[nH]1
CCc1cc2c([N+](=O)[O-])cccc2n1Cc1ccccc1
null
null
CN(C)C=O.O
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
16b46a8af20339f7ff0b611b4ac5dd01fe35ba577361e893c359dfa478dc1974
2e1e5fd9557b69cb528f6b2ffd179c67ef24ecb1a2c3994e1cdf0efe7ae19e9c
c1ccc(Cn2ccc3ccccc32)cc1
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[C:5]-[c:6]1:[c:7]:[c:8]:[c:9](:[c:10]):[nH;D2;+0:11]:1>>[C:5]-[c:6]1:[c:7]:[c:8]:[c:9](:[c:10]):[n;H0;D3;+0:11]:1-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4]
91
[{"value": 91.0, "product": "C1(=CC=CC=C1)CN1C(=CC2=C(C=CC=C12)[N+](=O)[O-])CC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 90.8, "product": "C1(=CC=CC=C1)CN1C(=CC2=C(C=CC=C12)[N+](=O)[O-])CC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
45
MINUTE
2-Ethyl-4-nitro-1H-indole (4.75 g, 25 mmol) was added to a mixture of 1.0 g (25 mmol) of 60% NaH/mineral oil (washed with hexane before adding DMF) in 40 ml DMF. After 45 minutes, 3.0 ml (25 mmol) of benzyl bromide was added. The mixture was stirred at room temperature for four hours, diluted with water, and extracted ...
10.6084/m9.figshare.5104873.v1
null
Primary halide
null
c1ccc2[nH]ccc2c1
c1cc2ccccc2[nH]1
c1cc2ccccc2[nH]1.c1ccccc1
HBr
CN(C)C=O.O
null
0.75
BrCc1ccccc1.CCc1cc2c([N+](=O)[O-])cccc2[nH]1>CN(C)C=O.O>CCc1cc2c([N+](=O)[O-])cccc2n1Cc1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-530aa127a76e4169b9ca650bd1dc8905
CCc1c(C(=O)C(N)=O)c2c([N+](=O)[O-])cccc2n1Cc1ccccc1>>CCc1c(C(=O)C(N)=O)c2c(N)cccc2n1Cc1ccccc1
C(C)C=1N(C2=CC=CC(=C2C1C(C(=O)N)=O)[N+](=O)[O-])CC1=CC=CC=C1.CCO>>NC1=C2C(=C(N(C2=CC=C1)CC1=CC=CC=C1)CC)C(C(=O)N)=O
O=[N+:12]([O-])[c:11]1[c:10]2[c:4]([C:5](=[O:6])[C:7]([NH2:8])=[O:9])[c:3]([CH2:2][CH3:1])[n:17]([CH2:18][c:19]3[cH:20][cH:21][cH:22][cH:23][cH:24]3)[c:16]2[cH:15][cH:14][cH:13]1>>[CH3:1][CH2:2][c:3]1[c:4]([C:5](=[O:6])[C:7]([NH2:8])=[O:9])[c:10]2[c:11]([NH2:12])[cH:13][cH:14][cH:15][c:16]2[n:17]1[CH2:18][c:19]1[cH:20]...
CCc1c(C(=O)C(N)=O)c2c([N+](=O)[O-])cccc2n1Cc1ccccc1
CCc1c(C(=O)C(N)=O)c2c(N)cccc2n1Cc1ccccc1
null
null
C1CCOC1
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
c1ccc(Cn2ccc3ccccc32)cc1
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]:[c:5]:[#7;a:6]>>[#7;a:6]:[c:5]:[c:4]:[c:2](-[NH2;D1;+0:1]):[c:3]
30.2
[{"value": 30.0, "product": "NC1=C2C(=C(N(C2=CC=C1)CC1=CC=CC=C1)CC)C(C(=O)N)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 30.2, "product": "NC1=C2C(=C(N(C2=CC=C1)CC1=CC=CC=C1)CC)C(C(=O)N)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
4
HOUR
A solution of 6.0 g (17.1 mmol) of 2-Ethyl-4-Nitro-α-oxo-1-(phenylmethyl)-1H-indole-3-acetamide in 140 ml of 1:1 THF:EtOH containing 1,0 g of 5% Pt/BaSO4 was hydrogenated at room temperature and 60 psi (4.22 Kg/cm2) for four hours. The catalyst was filtered and the filtrate evaporated in vacuo. The residue was chromato...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1cc2ccccc2[nH]1.c1ccccc1
Other
C1CCOC1
null
4
CCc1c(C(=O)C(N)=O)c2c([N+](=O)[O-])cccc2n1Cc1ccccc1>C1CCOC1>CCc1c(C(=O)C(N)=O)c2c(N)cccc2n1Cc1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-e62040325e0347dba1d20052ff7e6f97
CCc1c(C(=O)C(N)=O)c2c(N)cccc2n1Cc1ccccc1.COC(=O)CBr>>CCc1c(C(=O)C(N)=O)c2c(NCC(=O)OC)cccc2n1Cc1ccccc1
BrCC(=O)OC.NC1=C2C(=C(N(C2=CC=C1)CC1=CC=CC=C1)CC)C(C(=O)N)=O>>COC(CNC1=C2C(=C(N(C2=CC=C1)CC1=CC=CC=C1)CC)C(C(=O)N)=O)=O
[CH3:1][CH2:2][c:3]1[c:4]([C:5](=[O:6])[C:7]([NH2:8])=[O:9])[c:10]2[c:11]([NH2:12])[cH:18][cH:19][cH:20][c:21]2[n:22]1[CH2:23][c:24]1[cH:25][cH:26][cH:27][cH:28][cH:29]1.Br[CH2:13][C:14](=[O:15])[O:16][CH3:17]>>[CH3:1][CH2:2][c:3]1[c:4]([C:5](=[O:6])[C:7]([NH2:8])=[O:9])[c:10]2[c:11]([NH:12][CH2:13][C:14](=[O:15])[O:16...
CCc1c(C(=O)C(N)=O)c2c(N)cccc2n1Cc1ccccc1.COC(=O)CBr
CCc1c(C(=O)C(N)=O)c2c(NCC(=O)OC)cccc2n1Cc1ccccc1
null
null
CN(C)C=O.O
Heteroatom Alkylation and Arylation
N-alkylation of primary amines with alkyl halides
308780347cfd56717124ea78bf2bc5de380db774d7ce948246e279dfd7d8998b
d2327a8d30a39f085182e5e2f77f5b022ac99c077866b86103acfec639a8f73d
c1ccc(Cn2ccc3ccccc32)cc1
Br-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5].[#7;a:6]:[c:7]:[c:8]:[c:9](-[NH2;D1;+0:10]):[c:11]>>[#7;a:6]:[c:7]:[c:8]:[c:9](-[NH;D2;+0:10]-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5]):[c:11]
64
[{"value": 64.0, "product": "COC(CNC1=C2C(=C(N(C2=CC=C1)CC1=CC=CC=C1)CC)C(C(=O)N)=O)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 63.9, "product": "COC(CNC1=C2C(=C(N(C2=CC=C1)CC1=CC=CC=C1)CC)C(C(=O)N)=O)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
60
CELSIUS
0.5
HOUR
Methyl bromoacetate (0.07 ml, 0.78 mmol) was added to 250 mg (0.78 mmol) of 4-Amino-2-Ethyl-α-oxo-1-(phenylmethyl)-1H-indole-3-Acetamide in 4 ml of DMF, stirred at 60° C. for 0.5 hour, and then at room temperature for 20 hours. The mixture was diluted with water and extracted with EtOAc. The EtOAC solution was washed w...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester.Primary amine
Ester.Secondary amine
null
null
c1cc2ccccc2[nH]1.c1ccccc1
HBr
CN(C)C=O.O
60
0.5
CCc1c(C(=O)C(N)=O)c2c(N)cccc2n1Cc1ccccc1.COC(=O)CBr>CN(C)C=O.O>CCc1c(C(=O)C(N)=O)c2c(NCC(=O)OC)cccc2n1Cc1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-4cedd0f2818c450b8027d96b9714b239
CCc1c(C(=O)C(N)=O)c2c(NCC(=O)OC)cccc2n1Cc1ccccc1>>CCc1c(C(=O)C(N)=O)c2c(NCC(=O)O)cccc2n1Cc1ccccc1
COC(CNC1=C2C(=C(N(C2=CC=C1)CC1=CC=CC=C1)CC)C(C(=O)N)=O)=O.[OH-].[Na+].CO.Cl>>NC(C(=O)C1=C(N(C2=CC=CC(=C12)NCC(=O)O)CC1=CC=CC=C1)CC)=O
C[O:16][C:14]([CH2:13][NH:12][c:11]1[c:10]2[c:4]([C:5](=[O:6])[C:7]([NH2:8])=[O:9])[c:3]([CH2:2][CH3:1])[n:21]([CH2:22][c:23]3[cH:24][cH:25][cH:26][cH:27][cH:28]3)[c:20]2[cH:19][cH:18][cH:17]1)=[O:15]>>[CH3:1][CH2:2][c:3]1[c:4]([C:5](=[O:6])[C:7]([NH2:8])=[O:9])[c:10]2[c:11]([NH:12][CH2:13][C:14](=[O:15])[OH:16])[cH:17...
CCc1c(C(=O)C(N)=O)c2c(NCC(=O)OC)cccc2n1Cc1ccccc1
CCc1c(C(=O)C(N)=O)c2c(NCC(=O)O)cccc2n1Cc1ccccc1
null
null
CCOC(=O)C
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1ccc(Cn2ccc3ccccc32)cc1
C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
53
[{"value": 53.0, "product": "NC(C(=O)C1=C(N(C2=CC=CC(=C12)NCC(=O)O)CC1=CC=CC=C1)CC)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 52.7, "product": "NC(C(=O)C1=C(N(C2=CC=CC(=C12)NCC(=O)O)CC1=CC=CC=C1)CC)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
A mixture of 190 mg (0.48 mmol) of [[3-(Aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]amino]acetic acid methyl ester, 5 ml of 1N NaOH, and 15 ml of MeOH was refluxed 0.33 hour, cooled, and stirred at room temperature for 1 hour. EtOAc and aqueous HCl were added and the EtOAc layer was washed with brine, dried ...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1cc2ccccc2[nH]1.c1ccccc1
Other
CCOC(=O)C
null
1
CCc1c(C(=O)C(N)=O)c2c(NCC(=O)OC)cccc2n1Cc1ccccc1>CCOC(=O)C>CCc1c(C(=O)C(N)=O)c2c(NCC(=O)O)cccc2n1Cc1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-d7fa7aa712274215b5d8790b097c1874
CC(=O)c1cc(Nc2cc(C)nc(N)n2)cc(C(C)=O)c1.CI>>CC(=O)c1cc(Nc2cc(C)[n+](C)c(N)n2)cc(C(C)=O)c1.[I-]
NC1=NC(=CC(=N1)NC1=CC(=CC(=C1)C(C)=O)C(C)=O)C.CI>>[I-].NC1=[N+](C(=CC(=N1)NC1=CC(=CC(=C1)C(C)=O)C(C)=O)C)C
[CH3:1][C:2](=[O:3])[c:4]1[cH:5][c:6]([NH:7][c:8]2[cH:9][c:10]([CH3:11])[n:12][c:14]([NH2:15])[n:16]2)[cH:17][c:18]([C:19]([CH3:20])=[O:21])[cH:22]1.[CH3:13][I:23]>>[CH3:1][C:2](=[O:3])[c:4]1[cH:5][c:6]([NH:7][c:8]2[cH:9][c:10]([CH3:11])[n+:12]([CH3:13])[c:14]([NH2:15])[n:16]2)[cH:17][c:18]([C:19]([CH3:20])=[O:21])[cH:...
CC(=O)c1cc(Nc2cc(C)nc(N)n2)cc(C(C)=O)c1.CI
CC(=O)c1cc(Nc2cc(C)[n+](C)c(N)n2)cc(C(C)=O)c1.[I-]
null
null
C(C)#N.O1CCCC1
Functional Group Interconversion
OtherReaction
f6f373ff15af259a6a955d28c8e1504795e14c395f484b607df25a875abe05b3
f1bbf9aa3c82f5e49be9f6d53533b6bb152f359232b6d32090c168949766aa71
c1ccc(Nc2cc[nH+]cn2)cc1
[C;D1;H3:1]-[c:2]1:[c:3]:[c:4]:[#7;a:5]:[c:6](-[N;D1;H2:7]):[n;H0;D2;+0:8]:1.[CH3;D1;+0:9]-[I;H0;D1;+0:10]>>[C;D1;H3:1]-[c:2]1:[c:3]:[c:4]:[#7;a:5]:[c:6](-[N;D1;H2:7]):[n+;H0;D3:8]:1-[CH3;D1;+0:9].[I-;H0;D0:10]
null
[]
null
null
null
null
Compound No. 2, FIG. 1A: A suspension of Compound No. 11 (2-amino-4-(3,5-diacetylphenyl)amino-6-methylpyrimidine) (0.284 g), was suspended in 1:1 acetonitrile-tetrahydrofuran was treated with methyl iodide (2 mL) and heated at 40°-45° C. under a reflux condenser for 18 hr. Cooling and filtration gave 0.35 g of 2-amino-...
10.6084/m9.figshare.5104873.v1
null
null
null
c1cncnc1
C1=CN=C[NH+]=C1
c1ccccc1.C1=CN=C[NH+]=C1
null
C(C)#N.O1CCCC1
null
null
CC(=O)c1cc(Nc2cc(C)nc(N)n2)cc(C(C)=O)c1.CI>C(C)#N.O1CCCC1>CC(=O)c1cc(Nc2cc(C)[n+](C)c(N)n2)cc(C(C)=O)c1.[I-]
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-705eb0cf3a5441248217ccc079f91152
CC(=O)c1cc(N)cc(C(C)=O)c1.N#CNC(=N)N>>CC(=O)c1cc(NC(=N)NC(=N)N)cc(C(C)=O)c1
C(C)(=O)C=1C=C(N)C=C(C1)C(C)=O.C(#N)NC(=N)N.Cl>>Cl.C(C)(=O)C=1C=C(C=C(C1)C(C)=O)NC(=N)NC(=N)N
[CH3:1][C:2](=[O:3])[c:4]1[cH:5][c:6]([NH2:7])[cH:14][c:15]([C:16]([CH3:17])=[O:18])[cH:19]1.[C:8](=[NH:9])([NH:10][C:11]#[N:12])[NH2:13]>>[CH3:1][C:2](=[O:3])[c:4]1[cH:5][c:6]([NH:7][C:8](=[NH:9])[NH:10][C:11](=[NH:12])[NH2:13])[cH:14][c:15]([C:16]([CH3:17])=[O:18])[cH:19]1
CC(=O)c1cc(N)cc(C(C)=O)c1.N#CNC(=N)N
CC(=O)c1cc(NC(=N)NC(=N)N)cc(C(C)=O)c1
null
null
O
Heteroatom Alkylation and Arylation
OtherReaction
4fa302539962125b5afbc3b7c652c5f6ac0c848b65cc6ee9a8cc31fc37dac702
69bab17abd42218af70031a95089cb8497f520bead244a193d73e0f37115ac3b
c1ccccc1
[N;D1;H1:1]=[C;H0;D3;+0:2](-[NH2;D1;+0:3])-[#7:4]-[C;H0;D2;+0:5]#[N;H0;D1;+0:6].[NH2;D1;+0:7]-[c:8](:[c:9]):[c:10]>>[N;D1;H1:1]=[C;H0;D3;+0:2](-[#7:4]-[C;H0;D3;+0:5](-[NH2;D1;+0:3])=[NH;D1;+0:6])-[NH;D2;+0:7]-[c:8](:[c:9]):[c:10]
null
[]
null
null
null
null
Compound No. 12. A suspension of 3,5-diacetylaniline (0.531 g) in water (8 mL) was treated with cyanoguanidine (0.285 g) and conc. HCl (0.25 mL) and heated at reflux. After 6 hr the mixture was cooled and concentrated and 0.248 g of off-white solid was filtered out and dried to give N-(3,5-diacetylphenyl)biguanide hydr...
10.6084/m9.figshare.5104873.v1
null
Cyanamide.Primary amine.Primary amine
Primary amine.Secondary amine
null
null
c1ccccc1
null
O
null
null
CC(=O)c1cc(N)cc(C(C)=O)c1.N#CNC(=N)N>O>CC(=O)c1cc(NC(=N)NC(=N)N)cc(C(C)=O)c1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-f5ab73fd88e543f2b4cd602c407b93f7
CC(=O)c1cc(N)cc(C(C)=O)c1.Nc1nc(N)nc(Cl)n1>>CC(=O)c1cc(Nc2nc(N)nc(N)n2)cc(C(C)=O)c1
Cl.ClC1=NC(=NC(=N1)N)N.Cl.C(C)(=O)C=1C=C(N)C=C(C1)C(C)=O>>C(C)(=O)C=1C=C(C=C(C1)C(C)=O)NC1=NC(=NC(=N1)N)N
[CH3:1][C:2](=[O:3])[c:4]1[cH:5][c:6]([NH2:7])[cH:16][c:17]([C:18]([CH3:19])=[O:20])[cH:21]1.Cl[c:8]1[n:9][c:10]([NH2:11])[n:12][c:13]([NH2:14])[n:15]1>>[CH3:1][C:2](=[O:3])[c:4]1[cH:5][c:6]([NH:7][c:8]2[n:9][c:10]([NH2:11])[n:12][c:13]([NH2:14])[n:15]2)[cH:16][c:17]([C:18]([CH3:19])=[O:20])[cH:21]1
CC(=O)c1cc(N)cc(C(C)=O)c1.Nc1nc(N)nc(Cl)n1
CC(=O)c1cc(Nc2nc(N)nc(N)n2)cc(C(C)=O)c1
null
null
O
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
565b1b62b297a3b1aad544a4f6d7760fc3910e7d367c9719d0e48a6d3fe6c36e
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(Nc2ncncn2)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](-[N;D1;H2:4]):[#7;a:5]:[c:6]:[#7;a:7]:1.[NH2;D1;+0:8]-[c:9](:[c:10]):[c:11]>>[N;D1;H2:4]-[c:3]1:[#7;a:5]:[c:6]:[#7;a:7]:[c;H0;D3;+0:1](-[NH;D2;+0:8]-[c:9](:[c:10]):[c:11]):[#7;a:2]:1
62.5
[{"value": 62.5, "product": "C(C)(=O)C=1C=C(C=C(C1)C(C)=O)NC1=NC(=NC(=N1)N)N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Compound No. 13: A suspension of 3,5-diacetylaniline (1.95 g) in water (10 mL) was treated with 2-chloro-4,6-diamino-1,3,5-triazine (1.455 g) and concentrated HCl (0.1 mL) and heated at reflux for 20 min. After cooling the hydrochloride of Compound No. 13 separated as a white powder. This was filtered out, dissolved in...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ncncn1
c1ncncn1
c1ccccc1.c1ncncn1
HCl
O
null
null
CC(=O)c1cc(N)cc(C(C)=O)c1.Nc1nc(N)nc(Cl)n1>O>CC(=O)c1cc(Nc2nc(N)nc(N)n2)cc(C(C)=O)c1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-74a2ccfcddee49eb8680c2a9e7272626
CC(=O)c1cccc(Nc2cc(C)nc(N)n2)c1.CI>>CC(=O)c1cccc(Nc2cc(C)[n+](C)c(N)n2)c1.[I-]
C(C)(=O)C=1C=C(C=CC1)NC1=NC(=NC(=C1)C)N.CI>>[I-].C(C)(=O)C=1C=C(C=CC1)NC1=NC(=[N+](C(=C1)C)C)N
[CH3:1][C:2](=[O:3])[c:4]1[cH:5][cH:6][cH:7][c:8]([NH:9][c:10]2[cH:11][c:12]([CH3:13])[n:14][c:16]([NH2:17])[n:18]2)[cH:19]1.[CH3:15][I:20]>>[CH3:1][C:2](=[O:3])[c:4]1[cH:5][cH:6][cH:7][c:8]([NH:9][c:10]2[cH:11][c:12]([CH3:13])[n+:14]([CH3:15])[c:16]([NH2:17])[n:18]2)[cH:19]1.[I-:20]
CC(=O)c1cccc(Nc2cc(C)nc(N)n2)c1.CI
CC(=O)c1cccc(Nc2cc(C)[n+](C)c(N)n2)c1.[I-]
null
null
CC(=O)C
Functional Group Interconversion
OtherReaction
f6f373ff15af259a6a955d28c8e1504795e14c395f484b607df25a875abe05b3
f1bbf9aa3c82f5e49be9f6d53533b6bb152f359232b6d32090c168949766aa71
c1ccc(Nc2cc[nH+]cn2)cc1
[C;D1;H3:1]-[c:2]1:[c:3]:[c:4]:[#7;a:5]:[c:6](-[N;D1;H2:7]):[n;H0;D2;+0:8]:1.[CH3;D1;+0:9]-[I;H0;D1;+0:10]>>[C;D1;H3:1]-[c:2]1:[c:3]:[c:4]:[#7;a:5]:[c:6](-[N;D1;H2:7]):[n+;H0;D3:8]:1-[CH3;D1;+0:9].[I-;H0;D0:10]
null
[]
null
null
null
null
Compound No. 14: 4-(3-acetylphenyl)amino-2-amino-6methylpyrimidine, Compound No. 15, (0.968 g) was suspended in acetone (5 mL) containing methyl iodide (2 mL) was heated at reflux for 48 hr. Filtration after cooling gave 0.657 g of 4-(3-acetylphenyl)amino-2-amino-1,6-dimethylpyrimidinium iodide as a white powder, mp 23...
10.6084/m9.figshare.5104873.v1
null
null
null
c1cncnc1
C1=CN=C[NH+]=C1
c1ccccc1.C1=CN=C[NH+]=C1
null
CC(=O)C
null
null
CC(=O)c1cccc(Nc2cc(C)nc(N)n2)c1.CI>CC(=O)C>CC(=O)c1cccc(Nc2cc(C)[n+](C)c(N)n2)c1.[I-]
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-b3ee4c95f2d64d7599ce13045545da3c
CC(=O)c1cccc(N)c1.Cc1cc(Cl)nc(N)n1>>CC(=O)c1cccc(Nc2cc(C)nc(N)n2)c1
[OH-].[K+].NC=1C=C(C=CC1)C(C)=O.NC1=NC(=CC(=N1)Cl)C.Cl>>C(C)(=O)C=1C=C(C=CC1)NC1=NC(=NC(=C1)C)N
[CH3:1][C:2](=[O:3])[c:4]1[cH:5][cH:6][cH:7][c:8]([NH2:9])[cH:18]1.Cl[c:10]1[cH:11][c:12]([CH3:13])[n:14][c:15]([NH2:16])[n:17]1>>[CH3:1][C:2](=[O:3])[c:4]1[cH:5][cH:6][cH:7][c:8]([NH:9][c:10]2[cH:11][c:12]([CH3:13])[n:14][c:15]([NH2:16])[n:17]2)[cH:18]1
CC(=O)c1cccc(N)c1.Cc1cc(Cl)nc(N)n1
CC(=O)c1cccc(Nc2cc(C)nc(N)n2)c1
null
null
O
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
c38b7155556ff28144ae37859ff6668b20d59da60c705d26b158542b6d8385da
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(Nc2ccncn2)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](-[N;D1;H2:4]):[#7;a:5]:[c:6](-[C;D1;H3:7]):[c:8]:1.[NH2;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[C;D1;H3:7]-[c:6]1:[#7;a:5]:[c:3](-[N;D1;H2:4]):[#7;a:2]:[c;H0;D3;+0:1](-[NH;D2;+0:9]-[c:10](:[c:11]):[c:12]):[c:8]:1
78.5
[{"value": 78.5, "product": "C(C)(=O)C=1C=C(C=CC1)NC1=NC(=NC(=C1)C)N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Compound No. 15: A suspension of m-aminoacetophenone (2.7 g) and 2-amino-4-chloro-6-methylpyrimidine (2.87 g) in 40 mL water was treated with 1.7 mL concentrated HCl and heated at reflux for 1 hour. Addition of 40 mL 1N KOH gave a light buff solid, which was filtered out and dried to give 3.8 g 4-(3-acetylphenyl)amino-...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1cncnc1
c1cncnc1
c1ccccc1.c1cncnc1
HCl
O
null
null
CC(=O)c1cccc(N)c1.Cc1cc(Cl)nc(N)n1>O>CC(=O)c1cccc(Nc2cc(C)nc(N)n2)c1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-0b3c68dde58a4f4fbcd3c8750233eef7
CC(=O)c1cc(N)cc(C(C)=O)c1.Clc1ncnc2nc[nH]c12>>CC(=O)c1cc(Nc2ncnc3nc[nH]c23)cc(C(C)=O)c1
[OH-].[K+].ClC1=C2NC=NC2=NC=N1.Cl.C(C)(=O)C=1C=C(N)C=C(C1)C(C)=O>>C(C)(=O)C=1C=C(C=C(C1)C(C)=O)NC1=C2NC=NC2=NC=N1
[CH3:1][C:2](=[O:3])[c:4]1[cH:5][c:6]([NH2:7])[cH:17][c:18]([C:19]([CH3:20])=[O:21])[cH:22]1.Cl[c:8]1[n:9][cH:10][n:11][c:12]2[n:13][cH:14][nH:15][c:16]12>>[CH3:1][C:2](=[O:3])[c:4]1[cH:5][c:6]([NH:7][c:8]2[n:9][cH:10][n:11][c:12]3[n:13][cH:14][nH:15][c:16]23)[cH:17][c:18]([C:19]([CH3:20])=[O:21])[cH:22]1
CC(=O)c1cc(N)cc(C(C)=O)c1.Clc1ncnc2nc[nH]c12
CC(=O)c1cc(Nc2ncnc3nc[nH]c23)cc(C(C)=O)c1
null
null
O
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
cc3f24fffcaf974b16f52ce977955348405e93cb36102dc19c5151f40ad54b4f
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(Nc2ncnc3nc[nH]c23)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5]2:[#7;a:6]:[c:7]:[#7;a:8]:[c:9]:2:1.[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[c:12]:[c:11](-[NH;D2;+0:10]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5]2:[#7;a:6]:[c:7]:[#7;a:8]:[c:9]:2:1):[c:13]
90.4
[{"value": 90.4, "product": "C(C)(=O)C=1C=C(C=C(C1)C(C)=O)NC1=C2NC=NC2=NC=N1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
10
MINUTE
Compound No. 16: A suspension of 3,5-diacetylaniline (0.531 g) in water (10 mL) was treated with 6-chloropurine (0.464 g) and concentrated HCl (0.25 mL) and heated at reflux for 30 min. After cooling the mixture was treated with 6 mL of aqueous 1N KOH. The mixture was stirred for 10 min and the solid was filtered out, ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ncc2nc[nH]c2n1
c1ncc2nc[nH]c2n1
c1ccccc1.c1ncc2nc[nH]c2n1
HCl
O
null
0.166667
CC(=O)c1cc(N)cc(C(C)=O)c1.Clc1ncnc2nc[nH]c12>O>CC(=O)c1cc(Nc2ncnc3nc[nH]c23)cc(C(C)=O)c1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-123a12fd08654e45b37f1f604736d38c
BrCc1ccccc1.CCOC(=O)CC(C)=O>>CCOC(=O)CC(=O)CCc1ccccc1
C(C1=CC=CC=C1)Br.[H-].[Na+].C(CC(=O)C)(=O)OCC>>C(C)OC(CC(=O)CCC1=CC=CC=C1)=O
Br[CH2:10][c:11]1[cH:12][cH:13][cH:14][cH:15][cH:16]1.[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH2:6][C:7](=[O:8])[CH3:9]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH2:6][C:7](=[O:8])[CH2:9][CH2:10][c:11]1[cH:12][cH:13][cH:14][cH:15][cH:16]1
BrCc1ccccc1.CCOC(=O)CC(C)=O
CCOC(=O)CC(=O)CCc1ccccc1
null
null
C1CCOC1.CCCCCC
C-C Coupling
OtherReaction
e8b75e5efb691ecf3c9116420e15918cdd0fda7b899536fb179ed39cbdad1bc2
836e0f77354d9f44b98dde88e343d5cebbf81f14d452aa51d1e50ec699999492
c1ccccc1
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[#8:5]-[C:6](=[O;D1;H0:7])-[C:8]-[C:9](-[CH3;D1;+0:10])=[O;D1;H0:11]>>[#8:5]-[C:6](=[O;D1;H0:7])-[C:8]-[C:9](=[O;D1;H0:11])-[CH2;D2;+0:10]-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4]
null
[]
-10
CELSIUS
30
MINUTE
NaH (13.8 g, 0.6 mole) was washed twice with hexane (2×50 ml) and suspended in 250 ml of freshly distilled THF. Next ethyl acetoacetate (75 ml, excess) was added dropwise carefully while the receiving flask was cooled at -10° C. After the addition was complete, it was stirred at -10° C. for 2 hours and at room temperat...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ketone
Ketone
null
null
c1ccccc1
HBr
C1CCOC1.CCCCCC
-10
0.5
BrCc1ccccc1.CCOC(=O)CC(C)=O>C1CCOC1.CCCCCC>CCOC(=O)CC(=O)CCc1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-97c55ca915ef4418862fcb86ab30f5ed
CC1=C(C(=O)O)Cc2ccccc21.O=S(Cl)Cl>>CC1=C(C(=O)Cl)Cc2ccccc21
CC1=C(CC2=CC=CC=C12)C(=O)O.S(=O)(Cl)Cl>>CC1=C(CC2=CC=CC=C12)C(=O)Cl
O[C:4]([C:3]1=[C:2]([CH3:1])[c:13]2[c:8]([cH:9][cH:10][cH:11][cH:12]2)[CH2:7]1)=[O:5].O=S(Cl)[Cl:6]>>[CH3:1][C:2]1=[C:3]([C:4](=[O:5])[Cl:6])[CH2:7][c:8]2[cH:9][cH:10][cH:11][cH:12][c:13]21
CC1=C(C(=O)O)Cc2ccccc21.O=S(Cl)Cl
CC1=C(C(=O)Cl)Cc2ccccc21
null
null
null
Functional Group Interconversion
Alcohol to chloride_SOCl2
c301c14a9dcd0670d52e8b77396cbe7fd8edeedd757bc43f4162ade1fc52fc93
787f545db5dc0b29dde55b5fbed7db8625b8055f49327f97ed4d83cc47c3af1d
C1=Cc2ccccc2C1
Cl-S(=O)-[Cl;H0;D1;+0:1].O-[C;H0;D3;+0:2](=[O;D1;H0:3])-[C:4](=[C:5](-[C;D1;H3:6])-[c:7])-[C:8]>>[C:8]-[C:4](-[C;H0;D3;+0:2](-[Cl;H0;D1;+0:1])=[O;D1;H0:3])=[C:5](-[C;D1;H3:6])-[c:7]
null
[]
null
null
null
null
1.0 g of 3-methylindene-2-carboxylic acid and 5 ml thionyl chloride were refluxed for 4 hours. Careful removal of the solvent by distillation under reduced pressure gave 3-methylindene-2-oyl chloride. The acid chloride dissolved in THF was dropped into a mixture of guanidine and sodium hydroxide at room temperature ove...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid
Acyl halide
null
null
C1=Cc2ccccc2C1
HCl
null
null
null
CC1=C(C(=O)O)Cc2ccccc21.O=S(Cl)Cl>>CC1=C(C(=O)Cl)Cc2ccccc21
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-234d9f67d5bc456d83ed16d8d4de410c
CCOC(=O)Cl.O=C1CCc2ccccc21>>CCOC(=O)C1Cc2ccccc2C1=O
C1(CCC2=CC=CC=C12)=O.C(CCC)[Li].ClC(=O)OCC>>C(=O)(OCC)C1C(C2=CC=CC=C2C1)=O
Cl[C:4]([O:3][CH2:2][CH3:1])=[O:5].[CH2:6]1[CH2:7][c:8]2[cH:9][cH:10][cH:11][cH:12][c:13]2[C:14]1=[O:15]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]1[CH2:7][c:8]2[cH:9][cH:10][cH:11][cH:12][c:13]2[C:14]1=[O:15]
CCOC(=O)Cl.O=C1CCc2ccccc21
CCOC(=O)C1Cc2ccccc2C1=O
null
null
C1CCOC1
C-C Coupling
OtherReaction
b0a5f5f290e5c12fb11be71000c002bcdea12c9d72177ea1938da57ba51b3784
f78bb7d35ddd1449899d9ed779d19c78d02ee4567d7058af2b421741fd5818d2
O=C1CCc2ccccc21
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#8:3]-[C:4].[O;D1;H0:5]=[C:6]1-[CH2;D2;+0:7]-[C:8]-[c:9]:[c:10]-1>>[C:4]-[#8:3]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[CH;D3;+0:7]1-[C:8]-[c:9]:[c:10]-[C:6]-1=[O;D1;H0:5]
null
[]
-20
CELSIUS
45
MINUTE
1-Indanone (1.5 g, 11.36 mmols) was dissolved in dry THF in a three neck flask equipped with nitrogen inlet, septum and a guard tube. The flask was cooled to -20° C. for 10 minutes. Then butyl lithium (11.37 ml, 12.48 mmols) was added dropwise through the septum using the syringe. The reaction mixture was allowed to st...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Ketone
Ketone.Ester
c1ccc2c(c1)CCC2
c1ccc2c(c1)CCC2
c1ccc2c(c1)CCC2
HCl
C1CCOC1
-20
0.75
CCOC(=O)Cl.O=C1CCc2ccccc21>C1CCOC1>CCOC(=O)C1Cc2ccccc2C1=O
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-b6a54649e164413f940a06f93c2f9e8d
CCOC(=O)C1Cc2ccccc2C1=O>>CCOC(=O)C1=Cc2ccccc2C1
C(=O)(OCC)C1C(C2=CC=CC=C2C1)=O>>C1C(=CC2=CC=CC=C12)C(=O)OCC
O=[C:7]1[CH:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[CH2:14][c:13]2[c:8]1[cH:9][cH:10][cH:11][cH:12]2>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[C:6]1=[CH:7][c:8]2[cH:9][cH:10][cH:11][cH:12][c:13]2[CH2:14]1
CCOC(=O)C1Cc2ccccc2C1=O
CCOC(=O)C1=Cc2ccccc2C1
null
null
CO.[BH4-].[Na+]
Miscellaneous
OtherReaction
e414f0ca5ed080038ee89dbe3cd83303296907ec5c3e5aff0278dc8f995f117a
d0cb29f74e619dcc00fec504ad2e56043281b867cf4b0a815622ce66567392f1
C1=Cc2ccccc2C1
O=[C;H0;D3;+0:1]1-[CH;D3;+0:2](-[C:3](=[O;D1;H0:4])-[#8:5]-[C:6])-[C:7]-[c:8]:[c:9]-1:[c:10]>>[C:6]-[#8:5]-[C:3](=[O;D1;H0:4])-[C;H0;D3;+0:2]1=[CH;D2;+0:1]-[c:9](:[c:10]):[c:8]-[C:7]-1
null
[]
null
null
null
null
2-Carbethoxy-1-indanone was dissolved in dry methanol at room temperature, to which sodium borohydride was added in three lots while the reaction mixture was kept stirring. The reaction mixture was further stirred for 30 minutes, after which the solid was filtered and the filtrate was evaporated to dryness. The residue...
10.6084/m9.figshare.5104873.v1
null
Ketone
Ester
c1ccc2c(c1)CCC2
C1=Cc2ccccc2C1
C1=Cc2ccccc2C1
Other
CO.[BH4-].[Na+]
null
null
CCOC(=O)C1Cc2ccccc2C1=O>CO.[BH4-].[Na+]>CCOC(=O)C1=Cc2ccccc2C1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-490d143774ec4390a10e9b0953bb6484
CCCCCNC[C@@H]1CC[C@@H](CNCCCCC)CC1.CN(C)c1ccc(N=C=O)cc1>>CCCCCN(C[C@@H]1CC[C@@H](CN(CCCCC)C(=O)Nc2ccc(N(C)C)cc2)CC1)C(=O)Nc1ccc(N(C)C)cc1
C(CCCC)NC[C@@H]1CC[C@H](CC1)CNCCCCC.CN(C1=CC=C(C=C1)N=C=O)C>>CN(C1=CC=C(C=C1)NC(N(CCCCC)C[C@@H]1CC[C@H](CC1)CN(C(=O)NC1=CC=C(C=C1)N(C)C)CCCCC)=O)C
[CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][NH:6][CH2:7][C@H:8]1[CH2:9][CH2:10][C@H:11]([CH2:12][NH:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[CH2:31][CH2:32]1.[C:19](=[O:20])=[N:21][c:22]1[cH:23][cH:24][c:25]([N:26]([CH3:28])[CH3:33])[cH:29][cH:30]1>>[CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][N:6]([CH2:7][C@H:8]1[CH2:9][CH2:10][C@...
CCCCCNC[C@@H]1CC[C@@H](CNCCCCC)CC1.CN(C)c1ccc(N=C=O)cc1
CCCCCN(C[C@@H]1CC[C@@H](CN(CCCCC)C(=O)Nc2ccc(N(C)C)cc2)CC1)C(=O)Nc1ccc(N(C)C)cc1
null
null
C(C)#N.CCOCC
Aromatic Heterocycle Formation
OtherReaction
5ebc203e1c64fa87330062f7941396943f49aa4192cca3ea1ed2a05e2647f68c
bb423a2f04d7886357135cd179d5334129f095917bd9e365b4b0b3498b284c57
O=C(NC[C@H]1CC[C@H](CNC(=O)Nc2ccccc2)CC1)Nc1ccccc1
[C;D1;H3:1]-[N;H0;D3;+0:2](-[CH3;D1;+0:3])-[c:4]1:[c:5]:[c:6]:[c:7](-[N;H0;D2;+0:8]=[C;H0;D2;+0:9]=[O;D1;H0:10]):[c:11]:[c:12]:1.[C:13]-[C:14]-[NH;D2;+0:15]-[C:16]-[C:17].[C:18]-[C:19]-[NH;D2;+0:20]-[C:21]-[C:22]>>[C:18]-[C:19]-[N;H0;D3;+0:20](-[C:21]-[C:22])-[C;H0;D3;+0:3](=[O;D1;H0:23])-[#7:24]-[c:25].[C:13]-[C:14]-[...
89
[{"value": 89.0, "product": "CN(C1=CC=C(C=C1)NC(N(CCCCC)C[C@@H]1CC[C@H](CC1)CN(C(=O)NC1=CC=C(C=C1)N(C)C)CCCCC)=O)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
10
HOUR
Trans-1,4-bis[(normalpentylamino)methyl]cyclohexane, 0.56 g, was dissolved in 10 ml of ether. A solution of 0.81 g of 4-dimethylaminophenyl isocyanate in 20 ml of acetonitrile was added. The reaction mixture was stirred at room temperature for 10 hours. The solvent of the reaction mixture was distilled off under reduce...
10.6084/m9.figshare.5104873.v1
null
Isocyanate.Secondary amine.Secondary amine.Tertiary amine
Urea.Urea.Tertiary amine.Tertiary amine
null
c1ccccc1
C1CCCCC1.c1ccccc1.c1ccccc1
Other
C(C)#N.CCOCC
null
10
CCCCCNC[C@@H]1CC[C@@H](CNCCCCC)CC1.CN(C)c1ccc(N=C=O)cc1>C(C)#N.CCOCC>CCCCCN(C[C@@H]1CC[C@@H](CN(CCCCC)C(=O)Nc2ccc(N(C)C)cc2)CC1)C(=O)Nc1ccc(N(C)C)cc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-a24726e74e5d4a6ca7abb5ec691259ae
O=C(Nc1ccc([N+](=O)[O-])cc1)N(C[C@@H]1CC[C@@H](CN(C(=O)Nc2ccc([N+](=O)[O-])cc2)C2CCCCC2)CC1)C1CCCCC1>>Nc1ccc(NC(=O)N(C[C@@H]2CC[C@@H](CN(C(=O)Nc3ccc(N)cc3)C3CCCCC3)CC2)C2CCCCC2)cc1
C1(CCCCC1)N(C(=O)NC1=CC=C(C=C1)[N+](=O)[O-])C[C@@H]1CC[C@H](CC1)CN(C(=O)NC1=CC=C(C=C1)[N+](=O)[O-])C1CCCCC1.[H][H]>>C1(CCCCC1)N(C(=O)NC1=CC=C(C=C1)N)C[C@@H]1CC[C@H](CC1)CN(C(=O)NC1=CC=C(C=C1)N)C1CCCCC1
O=[N+:1]([O-])[c:2]1[cH:3][cH:4][c:5]([NH:6][C:7](=[O:8])[N:9]([CH2:10][C@H:11]2[CH2:12][CH2:13][C@H:14]([CH2:15][N:16]([C:17](=[O:18])[NH:19][c:20]3[cH:21][cH:22][c:23]([N+:24](=O)[O-])[cH:25][cH:26]3)[CH:27]3[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]3)[CH2:33][CH2:34]2)[CH:35]2[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40]2)...
O=C(Nc1ccc([N+](=O)[O-])cc1)N(C[C@@H]1CC[C@@H](CN(C(=O)Nc2ccc([N+](=O)[O-])cc2)C2CCCCC2)CC1)C1CCCCC1
Nc1ccc(NC(=O)N(C[C@@H]2CC[C@@H](CN(C(=O)Nc3ccc(N)cc3)C3CCCCC3)CC2)C2CCCCC2)cc1
null
[Pd].[C].[Pd]
CN(C)C=O
Reduction
OtherReaction
6748a51a25102225412593c5a930e43f5a8904a80803177de025a6f83c59d65e
a303b0dfb15cc6bade463acf71681cf3ba7580b599dfa4d28d8caac83d08cd17
O=C(Nc1ccccc1)N(C[C@H]1CC[C@H](CN(C(=O)Nc2ccccc2)C2CCCCC2)CC1)C1CCCCC1
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4].O=[N+;H0;D3:5](-[O-])-[c:6](:[c:7]):[c:8]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4].[NH2;D1;+0:5]-[c:6](:[c:7]):[c:8]
106.6
[{"value": 95.0, "product": "C1(CCCCC1)N(C(=O)NC1=CC=C(C=C1)N)C[C@@H]1CC[C@H](CC1)CN(C(=O)NC1=CC=C(C=C1)N)C1CCCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 106.6, "product": "C1(CCCCC1)N(C(=O)NC1=CC=C(C=C1)N)C[C@@H]1CC[C@H](CC1)CN(C(=O)NC1=CC=C(C=C1)N)C1CCCCC1", "details": "CALCULATEDPERCENTYIELD", ...
null
null
null
null
A 0.6 g quantity of 10% palladium carbon was added to 100 ml of a DMF solution containing 5.7 g of trans-1,4-bis[[1-cyclohexyl-3-(4-nitrophenyl)ureido]-metyl]cyclohexane synthesized in accordance with Example 2. Hydrogen was added at ordinal pressure and normal temperature for 15 hours. After completion of the reaction...
10.6084/m9.figshare.5104873.v1
null
Nitro group.Nitro group
Primary amine.Primary amine
null
null
c1ccccc1.C1CCCCC1.c1ccccc1.C1CCCCC1.C1CCCCC1
Other
[Pd].[C].[Pd].CN(C)C=O
null
null
O=C(Nc1ccc([N+](=O)[O-])cc1)N(C[C@@H]1CC[C@@H](CN(C(=O)Nc2ccc([N+](=O)[O-])cc2)C2CCCCC2)CC1)C1CCCCC1>[Pd].[C].[Pd].CN(C)C=O>Nc1ccc(NC(=O)N(C[C@@H]2CC[C@@H](CN(C(=O)Nc3ccc(N)cc3)C3CCCCC3)CC2)C2CCCCC2)cc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-cf112f9f981e4357be02e4ddbd112b54
C#CCBr.CONC(=O)OC>>C#CCN(OC)C(=O)OC
O.[H-].[Na+].CONC(OC)=O.C(C#C)Br>>CON(C(OC)=O)CC#C
Br[CH2:3][C:2]#[CH:1].[NH:4]([O:5][CH3:6])[C:7](=[O:8])[O:9][CH3:10]>>[CH:1]#[C:2][CH2:3][N:4]([O:5][CH3:6])[C:7](=[O:8])[O:9][CH3:10]
C#CCBr.CONC(=O)OC
C#CCN(OC)C(=O)OC
null
null
O1CCCC1
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
5da873da5e065666521679df8db5a1d2754540edd93ae40997847c9a24dedeb3
c05cd517c346aa4e8e8e58218c491edaea33d354b5dba9eb90dac8ad97104f73
null
Br-[CH2;D2;+0:1]-[C:2]#[C;D1;H1:3].[C;D1;H3:4]-[#8:5]-[C:6](=[O;D1;H0:7])-[NH;D2;+0:8]-[#8:9]-[C;D1;H3:10]>>[C;D1;H1:3]#[C:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:8](-[#8:9]-[C;D1;H3:10])-[C:6](=[O;D1;H0:7])-[#8:5]-[C;D1;H3:4]
58.7
[{"value": 58.7, "product": "CON(C(OC)=O)CC#C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
0.43 g of sodium hydride (60% in oil) was suspended in 10 ml of tetrahydrofuran, and 1.0 g of methyl N-methoxycarbamate and 1.36 g of propargyl bromide were added to the suspension in this order while being cooled with ice. The mixture was heat-refluxed for 4 hours. After completion of the reaction, water was added to ...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Carbamic ester
Carbamic ester
null
null
null
HBr
O1CCCC1
null
null
C#CCBr.CONC(=O)OC>O1CCCC1>C#CCN(OC)C(=O)OC
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-b317ab1e31f1484d8c7fa6fc2ad9a7be
C#CCOCCl.CONC(=O)OC>>C#CCOCN(OC)C(=O)OC
O.[H-].[Na+].CONC(OC)=O.ClCOCC#C>>CON(C(OC)=O)COCC#C
Cl[CH2:5][O:4][CH2:3][C:2]#[CH:1].[NH:6]([O:7][CH3:8])[C:9](=[O:10])[O:11][CH3:12]>>[CH:1]#[C:2][CH2:3][O:4][CH2:5][N:6]([O:7][CH3:8])[C:9](=[O:10])[O:11][CH3:12]
C#CCOCCl.CONC(=O)OC
C#CCOCN(OC)C(=O)OC
null
null
O1CCCC1
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
86848dd2159c6006fdcfad1637821bff7ec5e51fc9ab33fa406eeb0ccd5d29e2
b12b7f91cf142e2ddad8d1f02ba972615b69f606a979e2c6ca26037ba95d3adf
null
Cl-[CH2;D2;+0:1]-[#8:2]-[C:3]-[C:4]#[C;D1;H1:5].[C;D1;H3:6]-[#8:7]-[C:8](=[O;D1;H0:9])-[NH;D2;+0:10]-[#8:11]-[C;D1;H3:12]>>[C;D1;H1:5]#[C:4]-[C:3]-[#8:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:10](-[#8:11]-[C;D1;H3:12])-[C:8](=[O;D1;H0:9])-[#8:7]-[C;D1;H3:6]
75.9
[{"value": 75.9, "product": "CON(C(OC)=O)COCC#C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
0.37 g of sodium hydride (60% in oil) was suspended in 10 ml of tetrahydrofuran, and 0.8 g of methyl N-methoxycarbamate and 0.96 g of chloromethylpropargyl ether were added thereto in this order while being cooled with ice. The mixture was heat-refluxed for 1 hour. After completion of the reaction, water was added to t...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Carbamic ester
Carbamic ester.Ether
null
null
null
HCl
O1CCCC1
null
null
C#CCOCCl.CONC(=O)OC>O1CCCC1>C#CCOCN(OC)C(=O)OC
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-70e031461ff64ee8941f84d430c91d71
C#CCBr.CONC(=O)c1ccc(Cl)cc1>>C#CCN(OC)C(=O)c1ccc(Cl)cc1
O.[H-].[Na+].CONC(C1=CC=C(C=C1)Cl)=O.C(C#C)Br>>CON(C(C1=CC=C(C=C1)Cl)=O)CC#C
Br[CH2:3][C:2]#[CH:1].[NH:4]([O:5][CH3:6])[C:7](=[O:8])[c:9]1[cH:10][cH:11][c:12]([Cl:13])[cH:14][cH:15]1>>[CH:1]#[C:2][CH2:3][N:4]([O:5][CH3:6])[C:7](=[O:8])[c:9]1[cH:10][cH:11][c:12]([Cl:13])[cH:14][cH:15]1
C#CCBr.CONC(=O)c1ccc(Cl)cc1
C#CCN(OC)C(=O)c1ccc(Cl)cc1
null
null
O1CCCC1
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
db9b1b8804b469c037e0a5ba95031d33e73dcd5fc2a6fa79163c623adf75f2a1
4a6c1e88c9e8bed487b746792f88d478ff36cc235f9a217d4632e6babdebdc9a
c1ccccc1
Br-[CH2;D2;+0:1]-[C:2]#[C;D1;H1:3].[C;D1;H3:4]-[#8:5]-[NH;D2;+0:6]-[C:7](=[O;D1;H0:8])-[c:9]>>[C;D1;H1:3]#[C:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:6](-[#8:5]-[C;D1;H3:4])-[C:7](=[O;D1;H0:8])-[c:9]
36.5
[{"value": 36.5, "product": "CON(C(C1=CC=C(C=C1)Cl)=O)CC#C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
0.22 g of sodium hydride (60% in oil) was suspended in 10 ml of tetrahydrofuran, and 1.0 g of N-methoxy-p-chlorobenzamide and 0.68 g of propargyl bromide were added thereto in this order while being cooled with ice. The mixture was heat-refluxed for 8 hours. After completion of the reaction, water was added to the reac...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amide
Tertiary amide
null
null
c1ccccc1
HBr
O1CCCC1
null
null
C#CCBr.CONC(=O)c1ccc(Cl)cc1>O1CCCC1>C#CCN(OC)C(=O)c1ccc(Cl)cc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-bc47ddbc82764811b755545cf676a4fc
C#CCBr.CONC(=O)c1ccc(Cl)cc1Cl>>C#CCOC(=NOC)c1ccc(Cl)cc1Cl
CONC(C1=C(C=C(C=C1)Cl)Cl)=O.C([O-])([O-])=O.[K+].[K+].C(C#C)Br.CN(C=O)C>>CON=C(C1=C(C=C(C=C1)Cl)Cl)OCC#C
Br[CH2:3][C:2]#[CH:1].[O:4]=[C:5]([NH:6][O:7][CH3:8])[c:9]1[cH:10][cH:11][c:12]([Cl:13])[cH:14][c:15]1[Cl:16]>>[CH:1]#[C:2][CH2:3][O:4][C:5](=[N:6][O:7][CH3:8])[c:9]1[cH:10][cH:11][c:12]([Cl:13])[cH:14][c:15]1[Cl:16]
C#CCBr.CONC(=O)c1ccc(Cl)cc1Cl
C#CCOC(=NOC)c1ccc(Cl)cc1Cl
null
null
O
Acylation
OtherReaction
a42fe6037e9428fb86a68610b95d04d1c80e76840fbd22ac5b494b61dddf5c16
1980a023362fbf7fcc752a926f2a644585c21669c0ad54dda0839f321f10887e
c1ccccc1
Br-[CH2;D2;+0:1]-[C:2]#[C;D1;H1:3].[C;D1;H3:4]-[#8:5]-[NH;D2;+0:6]-[C;H0;D3;+0:7](=[O;H0;D1;+0:8])-[c:9](:[c:10]):[c:11]>>[C;D1;H1:3]#[C:2]-[CH2;D2;+0:1]-[O;H0;D2;+0:8]-[C;H0;D3;+0:7](=[N;H0;D2;+0:6]-[#8:5]-[C;D1;H3:4])-[c:9](:[c:10]):[c:11]
29.8
[{"value": 29.8, "product": "CON=C(C1=C(C=C(C=C1)Cl)Cl)OCC#C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3
HOUR
1.0 g of N-methoxy-2,4-dichlorobenzamide, 0.75 g of potassium carbonate and 0.65 g of propargyl bromide were added to 10 ml of N,N-dimethylformamide, and the mixture was stirred for 3 hours. After completion of the reaction, water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amide
Ether
null
null
c1ccccc1
HBr
O
null
3
C#CCBr.CONC(=O)c1ccc(Cl)cc1Cl>O>C#CCOC(=NOC)c1ccc(Cl)cc1Cl
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-78a2d25f14b9434b93e8ef7743620d47
C#CCOCCl.CONC(=O)c1ccccc1>>C#CCOCN(OC)C(=O)c1ccccc1
O.C([O-])([O-])=O.[K+].[K+].ClCOCC#C.CONC(C1=CC=CC=C1)=O>>CON(C(C1=CC=CC=C1)=O)COCC#C
Cl[CH2:5][O:4][CH2:3][C:2]#[CH:1].[NH:6]([O:7][CH3:8])[C:9](=[O:10])[c:11]1[cH:12][cH:13][cH:14][cH:15][cH:16]1>>[CH:1]#[C:2][CH2:3][O:4][CH2:5][N:6]([O:7][CH3:8])[C:9](=[O:10])[c:11]1[cH:12][cH:13][cH:14][cH:15][cH:16]1
C#CCOCCl.CONC(=O)c1ccccc1
C#CCOCN(OC)C(=O)c1ccccc1
null
null
C(C)#N
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
0babe25fdcc7557d9a098e60c4e2635197f8146663a5ec9ff74cb717c3ce944e
079d538bb08fcdef8e7b0c806871ec3b6fd57947885e03a54265bebefeb48ca6
c1ccccc1
Cl-[CH2;D2;+0:1]-[#8:2]-[C:3]-[C:4]#[C;D1;H1:5].[C;D1;H3:6]-[#8:7]-[NH;D2;+0:8]-[C:9](=[O;D1;H0:10])-[c:11]>>[C;D1;H1:5]#[C:4]-[C:3]-[#8:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:8](-[#8:7]-[C;D1;H3:6])-[C:9](=[O;D1;H0:10])-[c:11]
91.9
[{"value": 91.9, "product": "CON(C(C1=CC=CC=C1)=O)COCC#C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3
HOUR
0.6 g of N-methoxybenzamide was dissolved in 10 ml of acetonitrile, and 0.55 g of potassium carbonate and 0.42 g of chloromethylpropargyl ether were added thereto in this order. The mixture was stirred at room temperature for 3 hours. After completion of the reaction, water was added to the reaction solution, and the m...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ether.Secondary amide
Ether.Tertiary amide
null
null
c1ccccc1
HCl
C(C)#N
null
3
C#CCOCCl.CONC(=O)c1ccccc1>C(C)#N>C#CCOCN(OC)C(=O)c1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-8a7f1a41a70a4d3db418869aba312fea
C#CCOCCl.CONS(=O)(=O)c1ccccc1>>C#CCOCN(OC)S(=O)(=O)c1ccccc1
O.C([O-])([O-])=O.[K+].[K+].ClCOCC#C.CONS(=O)(=O)C1=CC=CC=C1>>CON(S(=O)(=O)C1=CC=CC=C1)COCC#C
Cl[CH2:5][O:4][CH2:3][C:2]#[CH:1].[NH:6]([O:7][CH3:8])[S:9](=[O:10])(=[O:11])[c:12]1[cH:13][cH:14][cH:15][cH:16][cH:17]1>>[CH:1]#[C:2][CH2:3][O:4][CH2:5][N:6]([O:7][CH3:8])[S:9](=[O:10])(=[O:11])[c:12]1[cH:13][cH:14][cH:15][cH:16][cH:17]1
C#CCOCCl.CONS(=O)(=O)c1ccccc1
C#CCOCN(OC)S(=O)(=O)c1ccccc1
null
null
C(C)#N
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
c9e6eec230201ae4d7e7b2e419ab36ef0222686e2de8e98691a9c34dce24ce9f
6e22d2d2df9145a05371d34e8f221134a49014314c48b65ae49b28ba1a406286
c1ccccc1
Cl-[CH2;D2;+0:1]-[#8:2]-[C:3]-[C:4]#[C;D1;H1:5].[C;D1;H3:6]-[#8:7]-[NH;D2;+0:8]-[#16:9](=[O;D1;H0:10])(=[O;D1;H0:11])-[c:12]>>[C;D1;H1:5]#[C:4]-[C:3]-[#8:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:8](-[#8:7]-[C;D1;H3:6])-[#16:9](=[O;D1;H0:10])(=[O;D1;H0:11])-[c:12]
85.6
[{"value": 85.6, "product": "CON(S(=O)(=O)C1=CC=CC=C1)COCC#C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
4
HOUR
0.6 g of N-methoxybenzenesulfonamide was dissolved in 10 ml of acetonitrile, and 0.44 g of potassium carbonate and 0.34 g of chloromethylpropargyl ether were added thereto in this order. The mixture was stirred at room temperature for 4 hours. After completion of the reaction, water was added to the reaction solution, ...
10.6084/m9.figshare.5104873.v1
null
Sulfonamide.Primary halide
Ether.Tertiary amine
null
null
c1ccccc1
HCl
C(C)#N
null
4
C#CCOCCl.CONS(=O)(=O)c1ccccc1>C(C)#N>C#CCOCN(OC)S(=O)(=O)c1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-45783ee212a64703af0373922cf64354
N#CCc1c(Cl)cccc1Cl.Nc1ncc(C=O)c(N)n1>>Nc1ncc2cc(-c3c(Cl)cccc3Cl)c(N)nc2n1
C(C)OCC[O-].[Na+].[Na].NC1=NC=C(C(=N1)N)C=O.ClC1=C(C(=CC=C1)Cl)CC#N>>NC=1N=CC2=C(N1)N=C(C(=C2)C2=C(C=CC=C2Cl)Cl)N
[CH2:7]([c:8]1[c:9]([Cl:10])[cH:11][cH:12][cH:13][c:14]1[Cl:15])[C:16]#[N:17].O=[CH:6][c:5]1[cH:4][n:3][c:2]([NH2:1])[n:20][c:19]1[NH2:18]>>[NH2:1][c:2]1[n:3][cH:4][c:5]2[cH:6][c:7](-[c:8]3[c:9]([Cl:10])[cH:11][cH:12][cH:13][c:14]3[Cl:15])[c:16]([NH2:17])[n:18][c:19]2[n:20]1
N#CCc1c(Cl)cccc1Cl.Nc1ncc(C=O)c(N)n1
Nc1ncc2cc(-c3c(Cl)cccc3Cl)c(N)nc2n1
null
null
C(C)OCCO
Aromatic Heterocycle Formation
OtherReaction
457efb65ee92bdd64de5e4c4637aa6a6f5956ef7df9875f74f905470843f8329
ee9b166152faf84f609712c2b467526aa08715073838c269f02320595214b178
c1ccc(-c2cnc3ncncc3c2)cc1
O=[CH;D2;+0:1]-[c:2]1:[c:3]:[#7;a:4]:[c:5]:[#7;a:6]:[c:7]:1-[NH2;D1;+0:8].[Cl;D1;H0:9]-[c:10](:[c:11]):[c;H0;D3;+0:12](-[CH2;D2;+0:13]-[C;H0;D2;+0:14]#[N;H0;D1;+0:15]):[c:16](-[Cl;D1;H0:17]):[c:18]>>[Cl;D1;H0:9]-[c:10](:[c:11]):[c;H0;D3;+0:12](-[c;H0;D3;+0:13]1:[cH;D2;+0:1]:[c:2]2:[c:3]:[#7;a:4]:[c:5]:[#7;a:6]:[c:7]:2:...
null
[]
null
null
null
null
(Prepared by the method of U.S. Pat. No. 3,534,039). To a solution of sodium 2-ethoxyethoxide prepared from 0.14 g of sodium and 60 mL of 2-ethoxyethanol was added 2.07 g of 2,4-diamino-5-pyrimidinecarboxaldehyde and 2.79 g of 2,6-dichlorophenylacetonitrile. The mixture is heated at reflux for 4 hours, cooled, and the ...
10.6084/m9.figshare.5104873.v1
null
Aldehyde.Nitrile.Primary amine
Primary amine
c1cncnc1
c1cnc2ncncc2c1
c1cnc2ncncc2c1.c1ccccc1
HO-
C(C)OCCO
null
null
N#CCc1c(Cl)cccc1Cl.Nc1ncc(C=O)c(N)n1>C(C)OCCO>Nc1ncc2cc(-c3c(Cl)cccc3Cl)c(N)nc2n1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-8859698c10bb4c7b910c576bf44215d1
CC(C)(C)N=C=O.Cc1ccccc1-c1cc2cnc(N)nc2nc1N>>Cc1ccccc1-c1cc2cnc(NC(=O)NC(C)(C)C)nc2nc1NC(=O)NC(C)(C)C
NC=1N=CC2=C(N1)N=C(C(=C2)C2=C(C=CC=C2)C)N.[H-].[Na+].C(C)(C)(C)N=C=O>>C(C)(C)(C)NC(=O)NC=1N=CC2=C(N1)N=C(C(=C2)C2=C(C=CC=C2)C)NC(=O)NC(C)(C)C
[C:15](=[O:16])=[N:17][C:18]([CH3:19])([CH3:30])[CH3:33].[CH3:1][c:2]1[cH:3][cH:4][cH:5][cH:6][c:7]1-[c:8]1[cH:9][c:10]2[cH:11][n:12][c:13]([NH2:14])[n:22][c:23]2[n:24][c:25]1[NH2:26]>>[CH3:1][c:2]1[cH:3][cH:4][cH:5][cH:6][c:7]1-[c:8]1[cH:9][c:10]2[cH:11][n:12][c:13]([NH:14][C:15](=[O:16])[NH:17][C:18]([CH3:19])([CH3:2...
CC(C)(C)N=C=O.Cc1ccccc1-c1cc2cnc(N)nc2nc1N
Cc1ccccc1-c1cc2cnc(NC(=O)NC(C)(C)C)nc2nc1NC(=O)NC(C)(C)C
null
null
CN(C=O)C
Acylation
OtherReaction
4cd4a24ba08f7bf502b3150ee8b2fb0c67292b0872d42e763884f695ebc3e7df
0ec38b10255bbfaa941365846c10b48228a0d7b15bea6d4efd05967a51aa7d5f
c1ccc(-c2cnc3ncncc3c2)cc1
[C;D1;H3:1]-[C;H0;D4;+0:2](-[CH3;D1;+0:3])(-[CH3;D1;+0:4])-[N;H0;D2;+0:5]=[C;H0;D2;+0:6]=[O;D1;H0:7].[NH2;D1;+0:8]-[c:9](:[#7;a:10]:[c:11]):[#7;a:12]:[c:13]:[#7;a:14]:[c:15](-[NH2;D1;+0:16]):[c:17]>>[C;D1;H3:1]-[C;H0;D4;+0:2](-[C;D1;H3:18])(-[C;D1;H3:19])-[NH;D2;+0:5]-[C;H0;D3;+0:6](=[O;D1;H0:7])-[NH;D2;+0:8]-[c:9](:[#...
null
[]
null
null
1.5
HOUR
A suspension of 0.5 g of 2,7-diamino-6-o-tolyl-pyrido[2,3-d]pyrimidine, prepared as described above in Example 1, in 10 mL of dimethylformamide is reacted with 0.16 g of 60% sodium hydride and stirred at ambient temperature for 1.5 hours. To the suspension is added 0.49 mL of t-butylisocyanate and the mixture stirred o...
10.6084/m9.figshare.5104873.v1
null
Isocyanate.Primary amine.Primary amine
Urea.Urea
null
null
c1ccccc1.c1cnc2ncncc2c1
Other
CN(C=O)C
null
1.5
CC(C)(C)N=C=O.Cc1ccccc1-c1cc2cnc(N)nc2nc1N>CN(C=O)C>Cc1ccccc1-c1cc2cnc(NC(=O)NC(C)(C)C)nc2nc1NC(=O)NC(C)(C)C
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-8ab3a8e6f55f47d8b365c3064b07de67
Nc1ncc2cc(-c3ccccc3)c(N)nc2n1.O=S(=O)([O-])OS(=O)(=O)[O-]>>Nc1ncc2cc(-c3ccccc3)c(O)nc2n1
Cl.S(=O)(=O)([O-])OS(=O)(=O)[O-].NC=1N=CC2=C(N1)N=C(C(=C2)C2=CC=CC=C2)N>>NC=1N=CC2=C(N1)N=C(C(=C2)C2=CC=CC=C2)O
N[c:14]1[c:7](-[c:8]2[cH:9][cH:10][cH:11][cH:12][cH:13]2)[cH:6][c:5]2[cH:4][n:3][c:2]([NH2:1])[n:18][c:17]2[n:16]1.O=S(=O)([O-])OS(=O)(=O)[O-:15]>>[NH2:1][c:2]1[n:3][cH:4][c:5]2[cH:6][c:7](-[c:8]3[cH:9][cH:10][cH:11][cH:12][cH:13]3)[c:14]([OH:15])[n:16][c:17]2[n:18]1
Nc1ncc2cc(-c3ccccc3)c(N)nc2n1.O=S(=O)([O-])OS(=O)(=O)[O-]
Nc1ncc2cc(-c3ccccc3)c(O)nc2n1
null
null
O
Heteroatom Alkylation and Arylation
OtherReaction
f03b70232ecf08fbaaf3a9634857fb15accb640e4f8168b323f472351503e508
0faab53fb44f5d790c940e8273c888214a6763f53a41b0c03d0241319b9333e9
c1ccc(-c2cnc3ncncc3c2)cc1
N-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]2:[#7;a:4]:[c:5]:[#7;a:6]:[c:7]:[c:8]:2:[c:9]:[c:10]:1-[c:11].O=S(=O)(-[O-;H0;D1:12])-O-S(=O)(=O)-[O-]>>[OH;D1;+0:12]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]2:[#7;a:4]:[c:5]:[#7;a:6]:[c:7]:[c:8]:2:[c:9]:[c:10]:1-[c:11]
null
[]
null
null
8
HOUR
To a solution of 2 L of concentrated HCl and 1 L of water is added 300 g of the disulfate salt of 2,7-diamino-6-phenylpyrido[2,3-d]pyrimidine and the resulting mixture refluxed with stirring overnight. The reaction mixture is cooled in an ice bath, filtered, and the insoluble product washed with water, followed by etha...
10.6084/m9.figshare.5104873.v1
null
Primary amine
Aromatic alcohol
c1cnc2ncncc2c1
c1cnc2ncncc2c1
c1cnc2ncncc2c1.c1ccccc1
HO-
O
null
8
Nc1ncc2cc(-c3ccccc3)c(N)nc2n1.O=S(=O)([O-])OS(=O)(=O)[O-]>O>Nc1ncc2cc(-c3ccccc3)c(O)nc2n1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-3fcd707cf920422c9a3f2c314bd98ea8
Nc1ncc2cc(-c3ccccc3)c(O)nc2n1>>CCCCNc1nc2nc(N)ncc2cc1-c1ccccc1
NC=1N=CC2=C(N1)N=C(C(=C2)C2=CC=CC=C2)O.ClCCl.S(=O)(Cl)Cl>>C(CCC)NC=1C(=CC2=C(N=C(N=C2)N)N1)C1=CC=CC=C1
O[c:6]1[n:5][c:8]2[n:9][c:10]([NH2:11])[n:12][cH:13][c:14]2[cH:15][c:16]1-[c:17]1[cH:18][cH:19][cH:1][cH:21][cH:22]1>>[CH3:1][CH2:2][CH2:3][CH2:4][NH:5][c:6]1[n:7][c:8]2[n:9][c:10]([NH2:11])[n:12][cH:13][c:14]2[cH:15][c:16]1-[c:17]1[cH:18][cH:19][cH:20][cH:21][cH:22]1
Nc1ncc2cc(-c3ccccc3)c(O)nc2n1
CCCCNc1nc2nc(N)ncc2cc1-c1ccccc1
null
null
CN(C=O)C
Miscellaneous
OtherReaction
3918fde530e82a2eb40ae9fd955cb7baf7502e7ebe185117a386e4aa64b46462
8acaf1912c506977ac2b93b637436f6e9f84e3c03a5886b7706de538665aeb49
c1ccc(-c2cnc3ncncc3c2)cc1
O-[c;H0;D3;+0:1]1:[n;H0;D2;+0:2]:[c;H0;D3;+0:3]2:[#7;a:4]:[c:5]:[#7;a:6]:[c:7]:[c:8]:2:[c:9]:[c:10]:1-[c:11]1:[c:12]:[cH;D2;+0:13]:[cH;D2;+0:14]:[cH;D2;+0:15]:[c:16]:1>>[CH3;D1;+0:14]-[C:17]-[C:18]-[C:19]-[NH;D2;+0:2]-[c;H0;D3;+0:1]1:[#7;a:20]:[c;H0;D3;+0:3]2:[#7;a:4]:[c:5]:[#7;a:6]:[c:7]:[c:8]:2:[c:9]:[c:10]:1-[c:11]1...
44.4
[{"value": 44.4, "product": "C(CCC)NC=1C(=CC2=C(N=C(N=C2)N)N1)C1=CC=CC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
5
HOUR
To a mixture of 23.8 g of 2-amino-6-phenyl-pyrido-[2,3-d]pyrimidin-7-ol prepared above in Example 8, 250 mL of dichloromethane, and 77.5 mL of dimethylformamide was added dropwise with cooling 36 mL of thionyl chloride keeping the temperature below 15° C. Following complete addition, the suspension was heated to reflux...
10.6084/m9.figshare.5104873.v1
null
Aromatic alcohol
Secondary amine
c1cnc2ncncc2c1.c1ccccc1
c1cnc2ncncc2c1.c1ccccc1
c1cnc2ncncc2c1.c1ccccc1
null
CN(C=O)C
null
5
Nc1ncc2cc(-c3ccccc3)c(O)nc2n1>CN(C=O)C>CCCCNc1nc2nc(N)ncc2cc1-c1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-e018a58eae26447a85248e2d7c5e33b2
CN(C)C=O.COc1ccc(-c2cc3cnc(N)nc3nc2O)cc1.O=S(Cl)Cl>>COc1ccc(-c2cc3cnc(N=CN(C)C)nc3nc2Cl)cc1
NC=1N=CC2=C(N1)N=C(C(=C2)C2=CC=C(C=C2)OC)O.ClCCl.CN(C=O)C.S(=O)(Cl)Cl>>ClC=1C(=CC2=C(N=C(N=C2)N=CN(C)C)N1)C1=CC=C(C=C1)OC
O=[CH:14][N:15]([CH3:16])[CH3:17].O[c:21]1[c:7](-[c:6]2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:24][cH:23]2)[cH:8][c:9]2[cH:10][n:11][c:12]([NH2:13])[n:18][c:19]2[n:20]1.O=S(Cl)[Cl:22]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6](-[c:7]2[cH:8][c:9]3[cH:10][n:11][c:12]([N:13]=[CH:14][N:15]([CH3:16])[CH3:17])[n:18][c:19]3[n:20][c:21]2...
CN(C)C=O.COc1ccc(-c2cc3cnc(N)nc3nc2O)cc1.O=S(Cl)Cl
COc1ccc(-c2cc3cnc(N=CN(C)C)nc3nc2Cl)cc1
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
38dc813b76ab9bfbc1c3f635b0be6bf536681495974807819197730cbd5961cd
1e7a2373d3de7893c523befcc507ddda1337e870f8d320e04e5a89e86694733f
c1ccc(-c2cnc3ncncc3c2)cc1
Cl-S(=O)-[Cl;H0;D1;+0:1].O-[c;H0;D3;+0:2]1:[#7;a:3]:[c:4]2:[#7;a:5]:[c:6](-[NH2;D1;+0:7]):[#7;a:8]:[c:9]:[c:10]:2:[c:11]:[c:12]:1-[c:13].O=[CH;D2;+0:14]-[#7:15](-[C;D1;H3:16])-[C;D1;H3:17]>>[C;D1;H3:16]-[#7:15](-[C;D1;H3:17])-[CH;D2;+0:14]=[N;H0;D2;+0:7]-[c:6]1:[#7;a:8]:[c:9]:[c:10]2:[c:11]:[c:12](-[c:13]):[c;H0;D3;+0:...
null
[]
null
null
6
HOUR
To a mixture of 67.0 g of 2-amino-6-(4-methoxy-phenyl)-pyrido[2,3-d]pyrimidin-7-ol from Example 10, 1 L of dichloromethane, and 155 mL of dimethylformamide was added dropwise with cooling 72 mL of thionyl chloride keeping the temperature below 15° C. The suspension was heated to reflux with stirring for 6 hours. The re...
10.6084/m9.figshare.5104873.v1
null
Tertiary amide.Aromatic alcohol.Primary amine
Aromatic halide
c1cnc2ncncc2c1
c1cnc2ncncc2c1
c1ccccc1.c1cnc2ncncc2c1
HCl
null
null
6
CN(C)C=O.COc1ccc(-c2cc3cnc(N)nc3nc2O)cc1.O=S(Cl)Cl>>COc1ccc(-c2cc3cnc(N=CN(C)C)nc3nc2Cl)cc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-86096de2e5674031bab10b49fa871e15
COc1ccc(-c2cc3cnc(N=CN(C)C)nc3nc2Cl)cc1>>COc1ccc(-c2cc3cnc(N)nc3nc2Cl)cc1
ClC=1C(=CC2=C(N=C(N=C2)N=CN(C)C)N1)C1=CC=C(C=C1)OC>>NC=1N=CC2=C(N1)N=C(C(=C2)C2=CC=C(C=C2)OC)Cl
CN(C)C=[N:13][c:12]1[n:11][cH:10][c:9]2[cH:8][c:7](-[c:6]3[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:20][cH:19]3)[c:17]([Cl:18])[n:16][c:15]2[n:14]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6](-[c:7]2[cH:8][c:9]3[cH:10][n:11][c:12]([NH2:13])[n:14][c:15]3[n:16][c:17]2[Cl:18])[cH:19][cH:20]1
COc1ccc(-c2cc3cnc(N=CN(C)C)nc3nc2Cl)cc1
COc1ccc(-c2cc3cnc(N)nc3nc2Cl)cc1
null
null
C(C)O
Deprotection
OtherReaction
33bcd42056000f3bc2d5907a85ff371ecf8a91697366ae3c95c7cdc536f4e4f7
09463156f8971f4e8007d84d8ed410eed1d618bdb6ba7dd05b4970ff2019f62b
c1ccc(-c2cnc3ncncc3c2)cc1
C-N(-C)-C=[N;H0;D2;+0:1]-[c:2](:[#7;a:3]:[c:4]):[#7;a:5]:[c:6]:[#7;a:7]>>[#7;a:7]:[c:6]:[#7;a:5]:[c:2](-[NH2;D1;+0:1]):[#7;a:3]:[c:4]
32.2
[{"value": 32.2, "product": "NC=1N=CC2=C(N1)N=C(C(=C2)C2=CC=C(C=C2)OC)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A mixture of 10 g of N'-(7-chloro-6-(4-methoxy-phenyl)-pyrido[2,3-d]pyrimidin-2-yl)-N,N-dimethyl-formamidine from Example 11 and 500 mL of 95% ethanol was refluxed for 3 hours. The solution was concentrated in vacuo and the precipitate collected by filtration. Crystallization from ethanol afforded 2.7 g of the title co...
10.6084/m9.figshare.5104873.v1
null
Tertiary amine
Primary amine
null
null
c1ccccc1.c1cnc2ncncc2c1
Other
C(C)O
null
null
COc1ccc(-c2cc3cnc(N=CN(C)C)nc3nc2Cl)cc1>C(C)O>COc1ccc(-c2cc3cnc(N)nc3nc2Cl)cc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-2f0d5340aaf840a58a389a03ef389f8c
CN.COc1ccc(-c2cc3cnc(N)nc3nc2Cl)cc1>>CNc1nc2nc(N)ncc2cc1-c1ccc(OC)cc1
NC=1N=CC2=C(N1)N=C(C(=C2)C2=CC=C(C=C2)OC)Cl.CN>>COC1=CC=C(C=C1)C1=CC2=C(N=C(N=C2)N)N=C1NC
[CH3:1][NH2:2].Cl[c:3]1[n:4][c:5]2[n:6][c:7]([NH2:8])[n:9][cH:10][c:11]2[cH:12][c:13]1-[c:14]1[cH:15][cH:16][c:17]([O:18][CH3:19])[cH:20][cH:21]1>>[CH3:1][NH:2][c:3]1[n:4][c:5]2[n:6][c:7]([NH2:8])[n:9][cH:10][c:11]2[cH:12][c:13]1-[c:14]1[cH:15][cH:16][c:17]([O:18][CH3:19])[cH:20][cH:21]1
CN.COc1ccc(-c2cc3cnc(N)nc3nc2Cl)cc1
CNc1nc2nc(N)ncc2cc1-c1ccc(OC)cc1
null
null
CO
Heteroatom Alkylation and Arylation
N-arylation (Buchwald-Hartwig/Ullmann-Goldberg)
95363dd4f7eaf5ca3b2b81ca3d4d6901dabfa76417ca700d29bf339c0c5e8fb0
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(-c2cnc3ncncc3c2)cc1
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]:[#7;a:4]):[c:5](-[c:6]):[c:7].[C;D1;H3:8]-[NH2;D1;+0:9]>>[#7;a:4]:[c:3]:[#7;a:2]:[c;H0;D3;+0:1](-[NH;D2;+0:9]-[C;D1;H3:8]):[c:5](-[c:6]):[c:7]
null
[]
null
null
null
null
A mixture of 3.4 g of 2-amino-7-chloro-6-(4-methoxyphenyl)-pyrido[2,3-d]pyrimidine from Example 12, 40 mL of anhydrous methylamine, and 10 mL of methanol were heated in a bomb on a steam bath for 4 hours. After cooling, the suspension was washed out of the bomb with 50 mL of methanol/water (50:50) and the solvents were...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1cnc2ncncc2c1
c1cnc2ncncc2c1
c1cnc2ncncc2c1.c1ccccc1
HCl
CO
null
null
CN.COc1ccc(-c2cc3cnc(N)nc3nc2Cl)cc1>CO>CNc1nc2nc(N)ncc2cc1-c1ccc(OC)cc1