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

HRID 1867615Notes

Reaction equation

HRID 1867615 reaction equation
[NH2:1][C@@H: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.[C:32]1([N:38]2[CH:42]=[C:41]([CH:43]3[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]3)[C:40](=[O:49])[NH:39]2)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.[O:50]1CCC[CH2:51]1>>[O:49]=[C:40]1[C:41]([CH:43]2[CH2:44][CH2:45][N:46]([C:51]([NH:1][C@@H:2]3[N:8]=[C:7]([C:9]4[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=4)[C:6]4[CH:15]=[CH:16][CH:17]=[CH:18][C:5]=4[N:4]([CH2:19][C:20]([F:21])([F:23])[F:22])[C:3]3=[O:24])=[O:50])[CH2:47][CH2:48]2)=[CH:42][N:38]([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[NH:39]1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 8471Triethylamine2×HCID 10854086HCID 10854086, compoundHCID 57979569HCID 57979569, compound

Product 1

HCID 117213544-(3-Oxo-1-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-N-[(3R)-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]piperidine-1-carboxamide

Procedure

(3R)-3-Amino-5-phenyl-1-(2,2,2-trifluoroethyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one (137 mg, 0.411 mmol) (Y.-J. Shi et al., Tetrahedron, 1999, 55, 909-918) and triethylamine (0.057 mL, 0.411 mmol) were added to a solution of p-nitrophenylchloroformate (83 mg, 0.411 mmol) in tetrahydrofuran (20 mL) at 0° C. After 1 h, 1-phenyl-4-piperidin-4-yl-1,2-dihydro-3H-pyrazol-3-one (50 mg, 0.205 mmol) and additional triethylamine (0.171 mL, 1.23 mmol) were added and the reaction warmed to ambient temperature and was then heated at 50° C. After 4 h, the reaction was concentrated and partitioned between ethyl acetate and saturated sodium bicarbonate. The organics were washed with water, brine, and dried over magnesium sulfate. Purification by silica gel chromatography (100% dichloromethane→10% methanol {1% ammonium hydroxide}/dichloromethane) gave the title compound (27 mg). MS 603.23 (M+1)

Workup

  1. temperaturewas then heated at 50° C
  2. waitAfter 4 h
  3. concentrationthe reaction was concentrated
  4. custompartitioned between ethyl acetate and saturated sodium bicarbonate
  5. washThe organics were washed with water, brine
  6. dry with materialdried over magnesium sulfate
  7. customPurification by silica gel chromatography (100% dichloromethane→10% methanol {1% ammonium hydroxide}/dichloromethane)

Sources & evidence

ORD record
ord-c1a3bbb98a194ac68392a5da5789ab26
Source dataset
uspto-grants-2009_12
Patent number
US07632832B2

Reaction notes

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