Tetrahydrofuran → (R)-4-(4-isopropyl-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 1867619Notes

Reaction equation

HRID 1867619 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.[CH:32]([C:35]1[NH:36][C:37](=[O:46])[N:38]([CH:40]2[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]2)[CH:39]=1)([CH3:34])[CH3:33].[O:47]1CCC[CH2:48]1>>[CH:32]([C:35]1[NH:36][C:37](=[O:46])[N:38]([CH:40]2[CH2:45][CH2:44][N:43]([C:48]([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:47])[CH2:42][CH2:41]2)[CH:39]=1)([CH3:34])[CH3:33]

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 8471Triethylamine2×HCID 10854086HCID 10854086, compoundHCID 579795744-Isopropyl-1-piperidin-4-yl-1,3-dihydro-2H-imidazol-2-one

Product 1

HCID 11570464(R)-4-(4-isopropyl-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

Procedure

(3R)-3-Amino-5-phenyl-1-(2,2,2-trifluoroethyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one (127 mg, 0.382 mmol) (Y.-J. Shi et al., Tetrahedron, 1999, 55, 909-918) and triethylamine (0.053 mL, 0.382 mmol) were added to a solution of p-nitrophenylchloroformate (77 mg, 0.382 mmol) in tetrahydrofuran (45 mL) at 0° C. After 1 h, additional triethylamine was added (0.106 mL, 0.764 mmol) along with 4-isopropyl-1-piperidin-4-yl-1,3-dihydro-2H-imidazol-2-one (80 mg, 0.382 mmol). The reaction stirred at 0 oC for 10 min and was then heated to 50oC. After 2 h, the reaction was concentrated and redissolved in ethyl acetate. The organics were 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 100 mg of the titled compound. MS 569.24 (M+1).

Workup

  1. temperaturewas then heated to 50oC
  2. waitAfter 2 h
  3. concentrationthe reaction was concentrated
  4. dissolutionredissolved in ethyl acetate
  5. washThe organics were washed 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-5595dee7043d4c66b8368e52e896ca78
Source dataset
uspto-grants-2009_12
Patent number
US07632832B2

Reaction notes

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