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

HRID 2093655Notes

Reaction equation

HRID 2093655 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(N(C(C)C)CC)(C)C.[F:42][C:43]([F:53])([F:52])[C:44]1[CH:51]=[CH:50][C:47]([CH2:48]Br)=[CH:46][CH:45]=1>ClCCl>[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]([CH2:48][C:47]6[CH:46]=[CH:45][C:44]([C:43]([F:42])([F:52])[F:53])=[CH:51][CH:50]=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

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 1230621-(Bromomethyl)-4-(trifluoromethyl)benzeneHCID 687456012-[4-(2,8-Diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-7-isopropyl-1,3-benzoxazole-5-carbonitrile

Product 1

HCID 251695867-Isopropyl-2-[4-({8-[4-(trifluoromethyl)benzyl]-2,8-diazaspiro[4.5]dec-2-yl}carbonyl)phenyl]-1,3-benzoxazole-5-carbonitrileYield 79%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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, EXAMPLE 121, Step B) in dichloromethane (2 ml) were added diisopropylethylamine (20 μl, 0.115 mmol) and 4-(trifluoromethyl)benzyl bromide (17 mg, 0.071 mmol). The mixture was stirred at room 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 (21.4 mg, 0.036 mmol, 79% yield). Mass spectrum (ESI) 587.3 (M+1).

Workup

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

Sources & evidence

ORD record
ord-ffd667bbe1c84a0da346dee4c4cf38ed
Source dataset
uspto-grants-2013_05
Patent number
US08445480B2

Reaction notes

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