2,2-Dimethylsuccinic anhydride → 2,2-Dimethyl-4-oxo-4-(4-{4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-[1,4]diazepan-1-yl)-butyric acid hydrochloride salt

HRID 1509872Notes

Reaction equation

HRID 1509872 reaction equation
[ClH:1].[N:2]1([C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]([C:18]3[N:19]=[C:20]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[O:21][C:22]=3[C:23]([F:26])([F:25])[F:24])=[O:17])=[CH:11][CH:10]=2)[CH2:8][CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.[CH3:33][C:34]1([CH3:41])[CH2:39][C:38](=[O:40])[O:37][C:35]1=[O:36]>C(Cl)Cl>[ClH:1].[CH3:33][C:34]([CH3:41])([CH2:39][C:38](=[O:40])[N:5]1[CH2:6][CH2:7][CH2:8][N:2]([C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]([C:18]3[N:19]=[C:20]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[O:21][C:22]=3[C:23]([F:26])([F:24])[F:25])=[O:17])=[CH:11][CH:10]=2)[CH2:3][CH2:4]1)[C:35]([OH:37])=[O:36]

Participants

4

Reactant 2

HCID 870672,2-Dimethylsuccinic anhydrideHCID 866388652-Phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid (4-[1,4]diazepan-1-yl-phenyl)-amide hydrochloride

Product 1

HCID 446228272,2-Dimethyl-4-oxo-4-(4-{4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-[1,4]diazepan-1-yl)-butyric acid hydrochloride saltYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid (4-[1,4]diazepan-1-yl-phenyl)-amide hydrochloride (35 mg, 0.075 mmol), methylene chloride (5 mL), and TEA (40 mg, 0.39 mmol) was stirred at room temperature. 2,2-Dimethylsuccinic anhydride (20 mg, 0.15 mmol) was added slowly. The reaction was stirred at room temperature for 0.5 hr then concentrated and the residue was taken up in ethyl acetate (50 mL) and washed with saturated ammonium chloride (50 mL), water (50 mL), and brine (20 mL). The solvent was removed and the residue was treated with hydrogen chloride in ether (1 N, 4 mL). The solid was filtered and washed with dry ether to afford 2,2-dimethyl-4-oxo-4-(4-{4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-[1,4]diazepan-1-yl)-butyric acid hydrochloride salt (35 mg, 85% yield). LCMS calcd for C28H29F3N4O5 (m/e) 558, observed 559 (M+H).

Workup

  1. stirringThe reaction was stirred at room temperature for 0.5 hr
  2. concentrationthen concentrated
  3. washwashed with saturated ammonium chloride (50 mL), water (50 mL), and brine (20 mL)
  4. customThe solvent was removed
  5. additionthe residue was treated with hydrogen chloride in ether (1 N, 4 mL)
  6. filtrationThe solid was filtered
  7. washwashed with dry ether

Sources & evidence

ORD record
ord-de29d7ea5faa4c10993a72cb2f6b615f
Source dataset
uspto-grants-2012_07
Patent number
US08211884B2

Reaction notes

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