Triethylamine → 1-(Cyclopropylmethyl)-3-(4-(1-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)piperidin-4-yloxy)phenyl)urea

HRID 515265ノート

反応式

HRID 515265 の反応式
[NH2:1][C:2]1[CH:31]=[CH:30][C:5]([O:6][CH:7]2[CH2:12][CH2:11][N:10]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([C:20]([OH:29])([C:25]([F:28])([F:27])[F:26])[C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=3)[CH2:9][CH2:8]2)=[CH:4][CH:3]=1.[C:32](Cl)(=O)[O:33]C1C=CC([N+]([O-])=O)=CC=1.[CH:45]1([CH2:48][NH2:49])[CH2:47][CH2:46]1.C(N(CC)CC)C>ClCCl.C(=O)(O)[O-].[Na+]>[CH:45]1([CH2:48][NH:49][C:32]([NH:1][C:2]2[CH:3]=[CH:4][C:5]([O:6][CH:7]3[CH2:12][CH2:11][N:10]([CH2:13][C:14]4[CH:15]=[CH:16][C:17]([C:20]([OH:29])([C:21]([F:22])([F:23])[F:24])[C:25]([F:28])([F:26])[F:27])=[CH:18][CH:19]=4)[CH2:9][CH2:8]3)=[CH:30][CH:31]=2)=[O:33])[CH2:47][CH2:46]1

参加物

7

反応物 4

HCID 8471TriethylamineHCID 75646CyclopropanemethanamineHCID 821294-Nitrophenyl chloroformateHCID 86670926HCID 86670926、化合物

生成物 1

HCID 866709271-(Cyclopropylmethyl)-3-(4-(1-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)piperidin-4-yloxy)phenyl)urea収率 22.7%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒2 回HCID 516892Sodium Bicarbonate溶媒

実験手順

A solution of 2-(4-((4-(4-aminophenoxy)piperidin-1-yl)methyl)phenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol (0.446 mmol, 200 mg) and 4-nitrophenyl carbonochloridate (0.446 mmol, 90 mg) in dichloromethane (1 mL) were stirred at room temperature for 30 minutes. Cyclopropylmethanamine (0.892 mmol, 0.091 mL, 63.4 mg) was added, followed by triethylamine (1.338 mmol, 0.187 mL, 135 mg) and the reaction stirred at room temperature overnight. The reaction mixture was diluted with dichloromethane and saturated sodium bicarbonate solution was added. The organic layer was separated and concentrated under vacuum. The residue was purified by silica column chromatography (eluent 2-8% methanol in dichloromethane) to give the title compound (55.3 mg). MS (ESI) m/z 546.2 [M+H]+

後処理

  1. additionwas added
  2. customThe organic layer was separated
  3. concentrationconcentrated under vacuum
  4. customThe residue was purified by silica column chromatography (eluent 2-8% methanol in dichloromethane)

出典と根拠

ORDレコード
ord-e34084d671af4d3cbfdbc7992cfcd254
出典データセット
uspto-grants-2015_08
特許番号
US09108939B2

反応ノート

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