1-Hydroxybenzotriazole → HCID 9829761, compound

HRID 1070481Notes

Reaction equation

HRID 1070481 reaction equation
[Cl:1][C:2]1[C:3]([C:29]2[CH2:34][CH2:33][CH2:32][CH2:31][CH:30]=2)=[CH:4][C:5]([O:27][CH3:28])=[C:6]([CH:26]=1)[C:7]([N:9]1[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[CH2:13][N:12]2[C:20]([C:23](O)=[O:24])=[CH:21][CH:22]=[C:11]2[CH2:10]1)=[O:8].[CH3:35][NH:36][CH2:37][C:38]1[CH:39]=[N:40][CH:41]=[CH:42][CH:43]=1.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>C(OCC)(=O)C>[Cl:1][C:2]1[C:3]([C:29]2[CH2:34][CH2:33][CH2:32][CH2:31][CH:30]=2)=[CH:4][C:5]([O:27][CH3:28])=[C:6]([CH:26]=1)[C:7]([N:9]1[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[CH2:13][N:12]2[C:20]([C:23]([N:36]([CH3:35])[CH2:37][C:38]3[CH:39]=[N:40][CH:41]=[CH:42][CH:43]=3)=[O:24])=[CH:21][CH:22]=[C:11]2[CH2:10]1)=[O:8]

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 883933-(Methylaminomethyl)pyridineHCID 10299280HCID 10299280, compound

Product 1

HCID 9829761HCID 9829761, compoundYield 92%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

10-(5-chloro-4-cyclohex-1-en-1-yl-2-methoxybenzoyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of Step G (0.125 g, 0.262 mmol), 3-(methylaminomethyl)pyridine (0.038 g, 0.314 mmol), 1-hydroxy benzotriazole (0.039 g, 0.288 mmol) and 1-[(3-dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.055 g, 0.288 mmol) were combined in amine-free N,N-dimethylformamide (1.1 mL), followed by addition of N,N-diisopropylethyl amine (0.068 mL, 0.393 mmol). The reaction was stirred at room temperature for 16 hours, then diluted with ethyl acetate and washed with water, saturated aqueous sodium bicarbonate and brine. The combined aqueous washings were saturated with sodium chloride and extracted with ethyl acetate. The combined organic phases were dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by flash column chromatography on silica gel eluting with 5% methanol in chloroform, and recrystallized from diethyl ether/pentane to afford 0.140 g of the title compound as a white crystalline solid, m.p. 178-179° C., 98.0% pure by analytical HPLC (Primesphere C-18, 2.0×150 mm, 45% acetonitrile/water, 0.2 mL/min.).

Workup

  1. washwashed with water, saturated aqueous sodium bicarbonate and brine
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined organic phases were dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash column chromatography on silica gel eluting with 5% methanol in chloroform
  7. customrecrystallized from diethyl ether/pentane

Sources & evidence

ORD record
ord-fdd2a07f2a18448783de9182ffb342ca
Source dataset
uspto-grants-2005_06
Patent number
US06903087B2

Reaction notes

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