Triethylamine → 2-cyclopropyl-5-methyl-7-[(3S)-3-(methylamino)pyrrolidin-1-yl]-6-phenyl-1,3-benzoxazole-4-carbonitrile

HRID 17578Notes

Reaction equation

HRID 17578 reaction equation
[CH:1]1([C:4]2[O:5][C:6]3[C:7](=[C:9]([C:21]#[N:22])[C:10]([CH3:20])=[C:11]([C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=4)[C:12]=3F)[N:8]=2)[CH2:3][CH2:2]1.C(N(CC)CC)C.[CH3:30][NH:31][C@H:32]1[CH2:36][CH2:35][NH:34][CH2:33]1.C(=O)([O-])O.[Na+]>CS(C)=O.C(OCC)(=O)C>[CH:1]1([C:4]2[O:5][C:6]3[C:7](=[C:9]([C:21]#[N:22])[C:10]([CH3:20])=[C:11]([C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=4)[C:12]=3[N:34]3[CH2:35][CH2:36][C@H:32]([NH:31][CH3:30])[CH2:33]3)[N:8]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 10261057(3S)-(-)-3-(Methylamino)pyrrolidineHCID 510414282-Cyclopropyl-7-fluoro-5-methyl-6-phenylbenzoxazole-4-carbonitrile

Product 1

HCID 510395212-cyclopropyl-5-methyl-7-[(3S)-3-(methylamino)pyrrolidin-1-yl]-6-phenyl-1,3-benzoxazole-4-carbonitrileYield 63%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

2-Cyclopropyl-7-fluoro-5-methyl-6-phenylbenzoxazole-4-carbonitrile (I-173) (250 mg, 0.86 mmol) was dissolved in dimethyl sulfoxide (5 ml), then at room temperature, triethylamine (155 μl, 1.11 mmol) and (3S)-3-(methylamino)pyrrolidine (119 μl, 1.11 mmol) were added. After stirred under nitrogen atmosphere at 90° C. for 13 hours, this was cooled to room temperature. The reaction liquid was fractionated with ethyl acetate and an aqueous saturated sodium hydrogencarbonate solution. The aqueous layer was further extracted twice with ethyl acetate. The organic layers were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The insoluble matter was separated by filtration, then the solvent was evaporated away, and the resulting residue was purified by preparative TLC (eluent, chloroform:methanol=93:7, v/v) to obtain the entitled compound (201 mg, 63%) as a white solid.

Workup

  1. temperaturethis was cooled to room temperature
  2. customThe reaction liquid
  3. extractionThe aqueous layer was further extracted twice with ethyl acetate
  4. washwashed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe insoluble matter was separated by filtration
  7. customthe solvent was evaporated away
  8. customthe resulting residue was purified by preparative TLC (eluent, chloroform

Sources & evidence

ORD record
ord-530bc1a4630040599ffcf1821cc43a98
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

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