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

HRID 1867616Notes

Reaction equation

HRID 1867616 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[CH2:42][CH:41]([C:43]3[CH:48]=[CH:47][N:46]=[CH:45][CH:44]=3)[NH:40][C:39]2=[O:49])[CH2:34][CH2:33]1.[O:50]1CCC[CH2:51]1>>[O:24]=[C:3]1[C@H:2]([NH:1][C:51]([N:32]2[CH2:33][CH2:34][CH:35]([N:38]3[CH2:42][CH:41]([C:43]4[CH:48]=[CH:47][N:46]=[CH:45][CH:44]=4)[NH:40][C:39]3=[O:49])[CH2:36][CH2:37]2)=[O:50])[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 10854086HCID 10854086, compoundHCID 579795681-Piperidin-4-yl-4-pyridin-4-ylimidazolidin-2-one

Product 1

HCID 115272874-(2-oxo-4-(pyridin-4-yl)imidazolidin-1-yl)-N-((R)-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 (49 mg, 0.146 mmol) (Y.-J. Shi et al., Tetrahedron, 1999, 55, 909-918) and triethylamine (0.020 mL, 0.146 mmol) were added to a solution of p-nitrophenylchloroformate (29 mg, 0.146 mmol) in tetrahydrofuran (5 mL) at 0 oC. After 1 h, 1-piperidin-4-yl-4-pyridin-4-ylimidazolidin-2-one (36 mg, 0.146 mmol) and additional triethylamine (0.040 mL, 0.292 mmol) were added and the reaction warmed to ambient temperature. After 16 h, the reaction was concentrated and partitioned between dichloromethane and saturated sodium bicarbonate. The organics were washed with water, brine, and dried over magnesium sulfate. Purification by silica gel chromatography (100% dichloromethane→15% methanol {1% ammonium hydroxide}/dichloromethane) gave the title compound (36 mg). MS 606.2 (M+1)

Workup

  1. waitAfter 16 h
  2. concentrationthe reaction was concentrated
  3. custompartitioned between dichloromethane and saturated sodium bicarbonate
  4. washThe organics were washed with water, brine
  5. dry with materialdried over magnesium sulfate
  6. customPurification by silica gel chromatography (100% dichloromethane→15% methanol {1% ammonium hydroxide}/dichloromethane)

Sources & evidence

ORD record
ord-720d78a52e394d37803074abdea2d8db
Source dataset
uspto-grants-2009_12
Patent number
US07632832B2

Reaction notes

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