Dimethyl Sulfoxide → 2-[2-(Benzyloxy)-1,1-dimethylethyl]-7-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrile

HRID 17318

Reaction equation

C(N(CC)CC)C.[CH3:8][N:9]([CH3:15])[C@H:10]1[CH2:14][CH2:13][NH:12][CH2:11]1.CS(C)=O.[CH2:20]([O:27][CH2:28][C:29]([C:32]1[O:33][C:34]2[C:35](=[C:37]([C:49]#[N:50])[C:38]([CH3:48])=[C:39]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[C:40]=2F)[N:36]=1)([CH3:31])[CH3:30])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>C(OCC)(=O)C>[CH2:20]([O:27][CH2:28][C:29]([C:32]1[O:33][C:34]2[C:35](=[C:37]([C:49]#[N:50])[C:38]([CH3:48])=[C:39]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[C:40]=2[N:12]2[CH2:13][CH2:14][C@H:10]([N:9]([CH3:15])[CH3:8])[CH2:11]2)[N:36]=1)([CH3:31])[CH3:30])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

Conditions

Temperature: 90 °C

Procedure

Triethylamine (222 μl, 1.59 mmol), (3S)-3-(dimethylamino)pyrrolidine (152 μl, 1.19 mmol) were added to a dimethyl sulfoxide (16.5 ml) solution of 2-[2-(benzyloxy)-1,1-dimethylethyl]-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrile (I-66) (330 mg, 0.796 mmol), followed by stirring overnight at 90° C. After cooling, the reaction liquid was diluted with ethyl acetate, washed three times with saturated brine, then dried over anhydrous magnesium sulfate, concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform:methanol=100:1) to obtain the entitled compound (369 mg, 91%) as a pale brown oil.

Workup

temperatureAfter cooling
customthe reaction liquid
washwashed three times with saturated brine
dry with materialdried over anhydrous magnesium sulfate
concentrationconcentrated under reduced pressure
customThe resulting residue was purified by silica gel column chromatography (chloroform:methanol=100:1)

Sources & evidence

ORD record: ord-4bf106d9387a4d12a650fb0b39fbb4e9
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07737166B2

Linked notes

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