Tetrahydrofuran → HCID 11685917, compound

HRID 1867627Notes

Reaction equation

HRID 1867627 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.[CH2:32]([CH:39]1[CH2:43][N:42]([CH:44]2[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]2)[C:41](=[O:50])[NH:40]1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.[O:51]1CCC[CH2:52]1>>[CH2:32]([CH:39]1[CH2:43][N:42]([CH:44]2[CH2:49][CH2:48][N:47]([C:52]([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:51])[CH2:46][CH2:45]2)[C:41](=[O:50])[NH:40]1)[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 8471Triethylamine2×HCID 10854086HCID 10854086, compoundHCID 57979565HCID 57979565, compound

Product 1

HCID 11685917HCID 11685917, compound

Procedure

(3R)-3-Amino-5-phenyl-1-(2,2,2-trifluoroethyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one (23 mg, 0.069 mmol) (Y.-J. Shi et al., Tetrahedron, 1999, 55, 909-918) and triethylamine (0.009 μL, 0.069 mmol) were added to a solution of p-nitrophenylchloroformate (14 mg, 0.069 mmol) in tetrahydrofuran (15 mL) at 0 oC. After 1 h, 4-benzyl-1-piperidin-4-ylimidazolidin-2-one (18 mg, 0.069 mmol) and additional triethylamine (0.027 mL, 0.207 mmol) were added and the reaction warmed to ambient temperature. After 16 h, the reaction was concentrated and partitioned between ethyl acetate and 1 N sodium hydroxide solution. The organics were washed with water, brine, and dried over magnesium sulfate. Purification by silica gel chromatography (100% dichloromethane=9% methanol {1% ammonium hydroxide}/dichloromethane) gave the title compound (30 mg). MS 619.6 (M+1)

Workup

  1. waitAfter 16 h
  2. concentrationthe reaction was concentrated
  3. custompartitioned between ethyl acetate and 1 N sodium hydroxide solution
  4. washThe organics were washed with water, brine
  5. dry with materialdried over magnesium sulfate
  6. customPurification by silica gel chromatography (100% dichloromethane=9% methanol {1% ammonium hydroxide}/dichloromethane)

Sources & evidence

ORD record
ord-8b714ff492464ac6ac421d363e7c3128
Source dataset
uspto-grants-2009_12
Patent number
US07632832B2

Reaction notes

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