Tetrahydrofuran → N-[(3R)-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]-4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxamide

HRID 459900Notes

Reaction equation

HRID 459900 reaction equation
[NH2:1][CH:2]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:6]2[CH:15]=[CH:16][CH:17]=[CH:18][C:5]=2[N:4]([CH2:19][C:20]([F:23])([F:22])[F:21])[C:3]1=[O:24].C(N(CC)CC)C.[NH:32]1[CH2:37][CH2:36][CH:35]([C:38]2[C:39](=[O:48])[NH:40][C:41]3[C:46]([CH:47]=2)=[CH:45][CH:44]=[CH:43][CH:42]=3)[CH2:34][CH2:33]1.[O:49]1CCC[CH2:50]1>>[O:24]=[C:3]1[C@H:2]([NH:1][C:50]([N:32]2[CH2:33][CH2:34][CH:35]([C:38]3[C:39](=[O:48])[NH:40][C:41]4[C:46]([CH:47]=3)=[CH:45][CH:44]=[CH:43][CH:42]=4)[CH2:36][CH2:37]2)=[O:49])[N:8]=[C:7]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:6]2[CH:15]=[CH:16][CH:17]=[CH:18][C:5]=2[N:4]1[CH2:19][C:20]([F:21])([F:23])[F:22]

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 8471Triethylamine2×HCID 107353833-Amino-5-phenyl-1-(2,2,2-trifluoroethyl)-1H-benzo[e][1,4]diazepin-2(3H)-oneHCID 183210463-(Piperidin-4-yl)quinolin-2(1H)-one

Product 1

HCID 11296242N-[(3R)-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]-4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxamide

Conditions

Temperature
0 °C

Procedure

3-Amino-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-1,4-benzodiazepine (25.6 mg, 0.0766 mmol) and p-nitrophenylchloroformate (15.3 mg, 0.0766 mmol) were dissolved in tetrahydrofuran (0.5 mL) under argon, and cooled to 0° C. Triethylamine (10.7 uL, 0.0766 mmol) was added and the reaction stirred for 1 h. Additional triethylamine was added (26.7 uL, 0.191 mmol) along with 3-(4-piperidinyl)quinolin-2-(1H)-one (17.5 mg, 0.0766 mmol). The reaction was warmed to room temperature and stirred overnight. The crude product was purified by reverse phase HPLC (C-18, 5% to 95% 0.1% trifluoroacetic acid/acetonitrile in 0.1% aqueous trifluoroacetic acid gradient elution) to give the title compound (30.2 mg). MS 588.2245 (M+1)

Workup

  1. temperatureThe reaction was warmed to room temperature
  2. stirringstirred overnight
  3. customThe crude product was purified by reverse phase HPLC (C-18, 5% to 95% 0.1% trifluoroacetic acid/acetonitrile in 0.1% aqueous trifluoroacetic acid gradient elution)

Sources & evidence

ORD record
ord-5f821bb069e54bf6883d162cf93af2b8
Source dataset
uspto-grants-2007_03
Patent number
US07196079B2

Reaction notes

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