Indole-2-carboxylic acid → HCID 14800376, compound

HRID 258102Notes

Reaction equation

HRID 258102 reaction equation
[C:1]([N:20]1[CH:24]=[C:23]([CH2:25][N:26]2[C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=3[C:30]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=3[F:43])=[N:29][C@@H:28]([NH2:44])[C:27]2=[O:45])[N:22]=[CH:21]1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:46]1[C:54]2[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=2)[CH:48]=[C:47]1[C:55](O)=[O:56].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(=O)(O)[O-].[Na+]>CN(C)C=O.O.C(OCC)(=O)C.C(N(CC)CC)C>[C:1]([N:20]1[CH:24]=[C:23]([CH2:25][N:26]2[C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=3[C:30]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=3[F:43])=[N:29][C@@H:28]([NH:44][C:55]([C:47]3[NH:46][C:54]4[C:49]([CH:48]=3)=[CH:50][CH:51]=[CH:52][CH:53]=4)=[O:56])[C:27]2=[O:45])[N:22]=[CH:21]1)([C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

10

Reactant 5

HCID 72899Indole-2-carboxylic acidHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 14800344HCID 14800344, compound

Product 1

HCID 14800376HCID 14800376, compoundYield 99.4%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (3R)-1,3-dihydro-1-(1-trityl-4-imidazolyl)methyl-3-amino-5-(2-fluorophenyl) -2H-1,4-benzodiazepine-2-one (0.81 g), indole-2-carboxylic acid (0.23 g), N-hydroxybenzotriazole (0.19 g) in N,N-dimethylformamide (8 ml) were added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.27 g) and triethylamine (0.14 g) under stirring at ambient temperature. The mixture was stirred for 4 hours at ambient temperature. To the reaction mixture were added ethyl acetate and water under stirring. The mixture was adjusted to pH 8 with an aqueous sodium bicarbonate. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The separated organic layer and the extract were combined, washed with water twice and dried over magnesium sulfate. The solvent was removed under reduced pressure to give (3R)-1,3-dihydro-1-(1-trityl-4-imidazolyl)methyl-3-(2-indolylcarbonylamino)-5-(2 -fluorophenyl)-2H-1,4-benzodiazepine-2-one (1.0 g).

Workup

  1. stirringThe mixture was stirred for 4 hours at ambient temperature
  2. stirringunder stirring
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with ethyl acetate
  5. washwashed with water twice
  6. dry with materialdried over magnesium sulfate
  7. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-dae10eeac3414b9c99673f8319d0a785
Source dataset
uspto-grants-1993_11
Patent number
US05264433

Reaction notes

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