Potassium Carbonate → 7-Isopropyl-2-[4-({8-[4-(trifluoromethyl)pyrimidin-2-yl]-2,8-diazaspiro[4.5]dec-2-yl}carbonyl)phenyl]-1,3-benzoxazole-5-carbonitrile

HRID 2093654Notes

Reaction equation

[CH2:1]1[C:5]2([CH2:10][CH2:9][NH:8][CH2:7][CH2:6]2)[CH2:4][CH2:3][N:2]1[C:11]([C:13]1[CH:18]=[CH:17][C:16]([C:19]2[O:20][C:21]3[C:27]([CH:28]([CH3:30])[CH3:29])=[CH:26][C:25]([C:31]#[N:32])=[CH:24][C:22]=3[N:23]=2)=[CH:15][CH:14]=1)=[O:12].C(=O)([O-])[O-].[K+].[K+].Cl[C:40]1[N:45]=[C:44]([C:46]([F:49])([F:48])[F:47])[CH:43]=[CH:42][N:41]=1>CO>[CH:28]([C:27]1[C:21]2[O:20][C:19]([C:16]3[CH:15]=[CH:14][C:13]([C:11]([N:2]4[CH2:3][CH2:4][C:5]5([CH2:10][CH2:9][N:8]([C:40]6[N:45]=[C:44]([C:46]([F:49])([F:48])[F:47])[CH:43]=[CH:42][N:41]=6)[CH2:7][CH2:6]5)[CH2:1]4)=[O:12])=[CH:18][CH:17]=3)=[N:23][C:22]=2[CH:24]=[C:25]([C:31]#[N:32])[CH:26]=1)([CH3:30])[CH3:29]

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of 2-[4-(2,8-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-7-isopropyl-1,3-benzoxazole-5-carbonitrile (25 mg, 0.046 mmol) in methanol (2 ml) were added potassium carbonate (13 mg, 0.094 mmol) and 2-chloro-4-(trifluoromethyl)pyrimidine (10 μl, 0.083 mmol). The mixture was heated to 50° C. and stirred at this temperature overnight, at which point LC/MS analysis showed a peak at the desired molecular weight. The reaction mixture was purified by flash chromatography on a Biotage Horizon, 25S column, eluting with 1 column volume of 100% dichloromethane followed by a gradient of 0 to 100% ethyl acetate in dichloromethane over 10 column volumes to provide the title compound (17.4 mg, 0.030 mmol, 65.7% yield). Mass spectrum (ESI) 575.2 (M+1).

Workup

customThe reaction mixture was purified by flash chromatography on a Biotage Horizon, 25S column
washeluting with 1 column volume of 100% dichloromethane

Sources & evidence

ORD record: ord-333d145bf79b43418b1fb3adb2f42f5e
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08445480B2

Reaction notes

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