Diisobutylaluminumhydride → (R)-4-(2-oxo-4-(pyridin-2-yl)-2,3-dihydroimidazol-1-yl)-N-(2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)piperidine-1-carboxamide

HRID 1867623Notes

Reaction equation

HRID 1867623 reaction equation
[H-].C([Al+]CC(C)C)C(C)C.[O:11]=[C:12]1[C@H:18]([NH:19][C:20]([N:22]2[CH2:27][CH2:26][CH:25]([NH:28][C:29]([NH:31][CH:32]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][N:39]=3)[C:33](OCC)=O)=[O:30])[CH2:24][CH2:23]2)=[O:21])[N:17]=[C:16]([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[C:15]2[CH:50]=[CH:51][CH:52]=[CH:53][C:14]=2[N:13]1[CH2:54][C:55]([F:58])([F:57])[F:56]>C1(C)C=CC=CC=1.ClCCl>[O:11]=[C:12]1[C@H:18]([NH:19][C:20]([N:22]2[CH2:23][CH2:24][CH:25]([N:28]3[CH:33]=[C:32]([C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][N:39]=4)[NH:31][C:29]3=[O:30])[CH2:26][CH2:27]2)=[O:21])[N:17]=[C:16]([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[C:15]2[CH:50]=[CH:51][CH:52]=[CH:53][C:14]=2[N:13]1[CH2:54][C:55]([F:58])([F:56])[F:57]

Participants

5

Reactant 2

HCID 21225700DiisobutylaluminumhydrideHCID 86620351Ethyl [({[1-({[(3R)-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]amino}carbonyl)piperidin-4-yl]amino}carbonyl)amino](pyridin-2-yl)acetate

Product 1

HCID 11541725(R)-4-(2-oxo-4-(pyridin-2-yl)-2,3-dihydroimidazol-1-yl)-N-(2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)piperidine-1-carboxamide

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

Diisobutylaluminum hydride (1M, 0.108 mL, 0.108 mmol) was added to a solution of ethyl [({[1-({[(3R)-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]amino}carbonyl)piperidin-4-yl]amino}carbonyl)amino](pyridin-2-yl)acetate (60 mg, 0.090 mmol) in toluene (4 mL) and dichloromethane (4 mL) at −78° C. and stirred for 30 min and then warmed to ambient temperature. After 4 h, the reaction was quenched with 1 N saturated potassium sodium tartrate solution and extracted with dichloromethane (2×). The combined organic extracts were dried over sodium sulfate, filtered, concentrated. Purification by silica gel chromatography (100% dichloromethane→10% methanol {1% ammonium hydroxide}/dichloromethane) gave the title compound. MS 604.2 (M+1)

Workup

  1. waitAfter 4 h
  2. customthe reaction was quenched with 1 N saturated potassium sodium tartrate solution
  3. extractionextracted with dichloromethane (2×)
  4. dry with materialThe combined organic extracts were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by silica gel chromatography (100% dichloromethane→10% methanol {1% ammonium hydroxide}/dichloromethane)

Sources & evidence

ORD record
ord-7598b80b76444a20baa588380349d157
Source dataset
uspto-grants-2009_12
Patent number
US07632832B2

Reaction notes

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