1-Hydroxybenzotriazole → HCID 10303235, compound

HRID 489577Notes

Reaction equation

HRID 489577 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][CH:38]([OH:41])[CH2:39][OH:40].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=N)C.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]([CH2:37][CH:38]([OH:41])[CH2:39][OH:40])[CH3:35])=[O:24])=[CH:21][CH:22]=[C:11]2[CH2:10]1)=[O:8]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27341223-(Methylamino)propane-1,2-diolHCID 10299280HCID 10299280, compoundHCID 21883477Ethylcarbodiimide hydrochloride

Product 1

HCID 10303235HCID 10303235, compoundYield 91.4%

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 Example 1, Step G (0.370 g, 0.776 mmol), 3-methylamino-1,2-propanediol (0.098 g, 0.931 mmol), 1-hydroxy benzotriazole (0.115 g, 0.854 mmol) and 1-[3-dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.164 g, 0.854 mmol) were combined in amine-free N,N-dimethylformamide (3.9 mL), followed by addition of N,N-diisopropylethylamine (0.202 mL, 1.16 mmol). The reaction was stirred at room temperature for 12 hours, then diluted with ethyl acetate and washed with 1 N hydrochloric acid, 1 N sodium hydeoxide 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 a solvent gradient from 0 to 5% of methanol in chloroform, to afford 0.400 g of the title compound as a white, crystalline solid, m.p.155-157° C.

Workup

  1. washwashed with 1 N hydrochloric acid, 1 N sodium hydeoxide 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 a solvent gradient from 0 to 5% of methanol in chloroform

Sources & evidence

ORD record
ord-c44892696c5c442f83b75cce3d6ad11c
Source dataset
uspto-grants-2005_12
Patent number
US06977254B2

Reaction notes

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