Tetrahydrofuran → HCID 11713729, compound

HRID 1867617Notes

Reaction equation

HRID 1867617 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.[O:32]=[C:33]1[NH:37][C:36]([C:38]#[N:39])=[CH:35][N:34]1[CH:40]1[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1.[O:46]1CCC[CH2:47]1>>[C:38]([C:36]1[NH:37][C:33](=[O:32])[N:34]([CH:40]2[CH2:45][CH2:44][N:43]([C:47]([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:46])[CH2:42][CH2:41]2)[CH:35]=1)#[N:39]

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 8471Triethylamine2×HCID 10854086HCID 10854086, compoundHCID 598565282-Oxo-1-piperidin-4-yl-2,3-dihydro-1H-imidazole-4-carbonitrile

Product 1

HCID 11713729HCID 11713729, compound

Procedure

(3R)-3-Amino-5-phenyl-1-(2,2,2-trifluoroethyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one (38 mg, 0.114 mmol) (Y.-J. Shi et al., Tetrahedron, 1999, 55, 909-918) and triethylamine (0.017 mL, 0.120 mmol) were added to a solution of p-nitrophenylchloroformate (23 mg, 0.114 mmol) in tetrahydrofuran (15 mL) at 0 oC. After 1 h, 2-oxo-1-piperidin-4-yl-2,3-dihydro-1H-imidazole-4-carbonitrile (23 mg, 0.120 mmol) and additional triethylamine (0.034 μL, 0.240 mmol) were added. The reaction warmed to ambient temperature and was then heated to 50 oC. After 2 h, the reaction was concentrated and then 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→7% methanol {1% ammonium hydroxide}/dichloromethane) gave the title compound (40 mg). MS 552.195 (M+1)

Workup

  1. temperaturewas then heated to 50 oC
  2. waitAfter 2 h
  3. concentrationthe reaction was concentrated
  4. custompartitioned between dichloromethane and saturated sodium bicarbonate
  5. washThe organics were washed with water, brine
  6. dry with materialdried over magnesium sulfate
  7. customPurification by silica gel chromatography (100% dichloromethane→7% methanol {1% ammonium hydroxide}/dichloromethane)

Sources & evidence

ORD record
ord-1fbfb7b0e31f4068836619a2bd9baf60
Source dataset
uspto-grants-2009_12
Patent number
US07632832B2

Reaction notes

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