Tetrahydrofuran → (R)-4-(2-oxo-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 1867626Notes

Reaction equation

HRID 1867626 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.[NH:32]1[CH2:37][CH2:36][CH:35]([N:38]2[CH:42]=[CH:41][NH:40][C:39]2=[O:43])[CH2:34][CH2:33]1.[O:44]1CCC[CH2:45]1>CN(C)C=O>[O:43]=[C:39]1[NH:40][CH:41]=[CH:42][N:38]1[CH:35]1[CH2:34][CH2:33][N:32]([C:45]([NH:1][C@@H:2]2[N:8]=[C:7]([C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:6]3[CH:15]=[CH:16][CH:17]=[CH:18][C:5]=3[N:4]([CH2:19][C:20]([F:21])([F:23])[F:22])[C:3]2=[O:24])=[O:44])[CH2:37][CH2:36]1

Participants

6

Reactant 4

HCID 8028Tetrahydrofuran3×HCID 8471TriethylamineHCID 10854086HCID 10854086, compoundHCID 128506021-(piperidin-4-yl)-2,3-dihydro-1H-imidazol-2-one

Product 1

HCID 11692206(R)-4-(2-oxo-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 1

HCID 6228DimethylformamideSolvent

Procedure

(3R)-3-Amino-5-phenyl-1-(2,2,2-trifluoroethyl) 1,3-dihydro-2H-1,4-benzodiazepin-2-one (199 mg, 0.598 mmol) (Y.-J. Shi et al., Tetrahedron, 1999, 55, 909-918) and triethylamine (83 uL, 0.598 mmol) in tetrahydrofuran (5 mL) were added to a solution of p-nitrophenylchloroformate (100 mg, 0.598 mmol) in tetrahydrofuran (15 mL) at 0 oC. After 1 h, 1-piperidin-4-yl-1,3-dihydro-2H-imidazol-2-one (100 mg, 0.598 mmol) in tetrahydrofuran (9 mL) and dimethylforamide (1 mL) were added and stirred at 0 oC for 10 min and then warned to room temperature. After 16 h, the reaction was concentrated and the residue dissolved in ethyl acetate, washed with 1 N sodium hydroxide solution (3×), water, brine, and dried over magnesium sulfate. Purification by silica gel chromatography (100% dichloromethane→10% methanol/dichloromethane) gave 70 mg of the titled compound. MS 527.5 (M+1).

Workup

  1. customwarned to room temperature
  2. waitAfter 16 h
  3. concentrationthe reaction was concentrated
  4. dissolutionthe residue dissolved in ethyl acetate
  5. washwashed with 1 N sodium hydroxide solution (3×), water, brine
  6. dry with materialdried over magnesium sulfate
  7. customPurification by silica gel chromatography (100% dichloromethane→10% methanol/dichloromethane)

Sources & evidence

ORD record
ord-78f3b6a2373d4bbea1b4242b3c34d05f
Source dataset
uspto-grants-2009_12
Patent number
US07632832B2

Reaction notes

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