1-Hydroxybenzotriazole → HCID 21947899, compound

HRID 2215158Notes

Reaction equation

HRID 2215158 reaction equation
Cl[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:13]([Cl:14])=[CH:12][C:11]([C:15]([N:17]2[C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=3[CH2:21][N:20]3[C:28]([C:31](O)=[O:32])=[CH:29][CH:30]=[C:19]3[CH2:18]2)=[O:16])=[C:10]([O:34][CH3:35])[CH:9]=1.[CH3:36][N:37]1[CH2:42][CH2:41][CH:40]([NH:43][CH3:44])[CH2:39][CH2:38]1.ON1C2C=CC=CC=2N=N1.[ClH:55].CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C>C(Cl)(Cl)Cl>[Cl:55][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:13]([Cl:14])=[CH:12][C:11]([C:15]([N:17]2[C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=3[CH2:21][N:20]3[C:28]([C:31]([N:43]([CH3:44])[CH:40]4[CH2:41][CH2:42][N:37]([CH3:36])[CH2:38][CH2:39]4)=[O:32])=[CH:29][CH:30]=[C:19]3[CH2:18]2)=[O:16])=[C:10]([O:34][CH3:35])[CH:9]=1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 5663231-Methyl-4-(methylamino)piperidineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10185723HCID 10185723, compound

Product 1

HCID 21947899HCID 21947899, compoundYield 33%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a stirred solution of 10-{[2′-chloro-6-chloro-3-methoxy-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of Example 16, Step C (0.250 g, 0.49 mmol) was added 1-methyl-4-(methylamino)piperidine (0.076 g, 0.59 mmol) followed by 1-hydroxybenzotriazole (0.073 g, 0.54 mmol), 1-[3-(dimethylamino)propyl]-3-ethyl carbodiimide hydrochloride (0.093 g, 0.54 mmol), and N,N-diisopropylethyl amine (0.096 g, 0.74 mmol). After stirring overnight, the reaction mixture was diluted with chloroform, washed with saturated aqueous sodium bicarbonate and brine, dried over anhydrous magnesium sulfate, filtered and evaporated to dryness. The residue was flash chromatographed over silica gel eluting with 5% methanol in chloroform containing 0.5% ammonium hydroxide, to provide the title compound as white powder (0.100 g), 92.95% pure by analytical HPLC [Primesphere C-18 column (2.0×150 mm); mobile phase:gradient from 10 to 90% acetonitrile/water containing 0.1% phosphoric acid, 2 to 20 minute gradient].

Workup

  1. washwashed with saturated aqueous sodium bicarbonate and brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. filtrationfiltered
  4. customevaporated to dryness
  5. customchromatographed over silica gel eluting with 5% methanol in chloroform containing 0.5% ammonium hydroxide

Sources & evidence

ORD record
ord-3fdbed008ad944eeaa41eda6f38d2b4d
Source dataset
uspto-grants-2006_09
Patent number
US07109193B2

Reaction notes

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