1-Hydroxybenzotriazole → HCID 10208562, compound

HRID 489583Notes

Reaction equation

HRID 489583 reaction equation
[C:1]1([C:7]2[CH:31]=[CH:30][C:10]([C:11]([N:13]3[C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=4[CH2:17][N:16]4[C:24]([C:27](O)=[O:28])=[CH:25][CH:26]=[C:15]4[CH2:14]3)=[O:12])=[CH:9][C:8]=2[CH3:32])[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1.Cl.[CH3:34][O:35][C:36](=[O:41])[C@@H:37]([CH2:39][OH:40])[NH2:38].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=N)C.C(N(CC)C(C)C)(C)C>C(OCC)(=O)C>[CH3:34][O:35][C:36](=[O:41])[C@H:37]([NH:38][C:27]([C:24]1[N:16]2[C:15]([CH2:14][N:13]([C:11](=[O:12])[C:10]3[CH:30]=[CH:31][C:7]([C:1]4[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=4)=[C:8]([CH3:32])[CH:9]=3)[C:19]3[CH:18]=[CH:23][CH:22]=[CH:21][C:20]=3[CH2:17]2)=[CH:26][CH:25]=1)=[O:28])[CH2:39][OH:40]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 10113257HCID 10113257, compoundHCID 11446470D-Serine methyl ester hydrochlorideHCID 21883477Ethylcarbodiimide hydrochloride

Product 1

HCID 10208562HCID 10208562, compoundYield 86.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

10-(4-Cyclohex-1-en-1-yl-3-methyl-benzoyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid (0.300 g, 0.703 mmol) of Example 5 Step E, D-serine methyl ester hydrochloride (0.131 g, 0.844 mmol), 1-hydroxy benzotriazole (0.104 g, 0.773 mmol) and 1-[3-dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.148 g, 0.773 mmol) were combined in amine-free N,N-dimethylformamide (2.8 mL), followed by the addition of N,N-diisopropylethylamine (0.307 mL, 1.76 mmol). The reaction was stirred at room temperature for 12 hours, then diluted with ethyl acetate and washed with water, 1 N hydrochloric acid, 1 N sodium hydroxide and brine. The combined aqueous washings were saturated with sodium chloride, and extracted with ethyl acetate. The organic phases were combined, dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by flash column chromatography on silica gel eluting with 10% methanol in chloroform, to afford 0.320 g of the title compound as a pale yellow solid.

Workup

  1. washwashed with water, 1 N hydrochloric acid, 1 N sodium hydroxide and brine
  2. extractionextracted with ethyl acetate
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash column chromatography on silica gel eluting with 10% methanol in chloroform

Sources & evidence

ORD record
ord-86acfdd8ec71465faaef2c758e318934
Source dataset
uspto-grants-2005_12
Patent number
US06977254B2

Reaction notes

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