1,1'-Carbonyldiimidazole → 5-(3,3-Difluorocyclobutyl)-3-[4-[4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl]bicyclo[2.2.2]oct-1-yl]-1,2,4-oxadiazole

HRID 639748ノート

反応式

HRID 639748 の反応式
[OH:1][N:2]=[C:3]([C:5]12[CH2:12][CH2:11][C:8]([C:13]3[N:17]([CH3:18])[C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[C:25]([F:28])([F:27])[F:26])=[N:15][N:14]=3)([CH2:9][CH2:10]1)[CH2:7][CH2:6]2)[NH2:4].[F:29][C:30]1([F:37])[CH2:33][CH:32]([C:34](O)=O)[CH2:31]1.C(N1C=CN=C1)(N1C=CN=C1)=O>C(Cl)Cl>[F:29][C:30]1([F:37])[CH2:33][CH:32]([C:34]2[O:1][N:2]=[C:3]([C:5]34[CH2:12][CH2:11][C:8]([C:13]5[N:17]([CH3:18])[C:16]([C:19]6[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=6[C:25]([F:28])([F:27])[F:26])=[N:15][N:14]=5)([CH2:9][CH2:10]3)[CH2:7][CH2:6]4)[N:4]=2)[CH2:31]1

参加物

5

反応物 3

HCID 682631,1'-CarbonyldiimidazoleHCID 137777893,3-Difluorocyclobutane-1-carboxylic acidHCID 72262919N-hydroxy-4-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}bicyclo[2.2.2]octane-1-carboximidamide

生成物 1

HCID 162223795-(3,3-Difluorocyclobutyl)-3-[4-[4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl]bicyclo[2.2.2]oct-1-yl]-1,2,4-oxadiazole

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

N′-Hydroxy-4-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}bicyclo[2.2.2]octane-1-carboximidamide (1-G) (120 mg, 0.305 mmol) was added to a pre-stirred solution of 3,3-difluorocyclobutanecarboxylic acid 2-D (166 mg, 1.22 mmol) and carbonyldiimidazole (198 mg, 1.22 mmol) in CH2Cl2 (8 ml). The resulting mixture was stirred at room temperature for 48 h, then concentrated. The solid was resuspended in toluene and refluxed under nitrogen atmosphere for 3 h. The product was purified by C-18 reverse phase HPLC eluting with 30-80% acetonitrile/water with 0.1% TFA to yield 2-E as a white powder. MS (ESI+)=494.2 (M+1); 1H NMR (500 MHz, CDCl3): δ 2.09 (6H, m), 2.31 (6H, m), 3.03-3.11 (4H, m), 3.57-3.61 (4H, m), 7.56 (1H, m), 7.71 (2H, m), 7.86 (1H, m) ppm. Shh-Light II Assay: IC50: 1.4 μM.

後処理

  1. concentrationconcentrated
  2. temperaturerefluxed under nitrogen atmosphere for 3 h
  3. customThe product was purified by C-18 reverse phase HPLC
  4. washeluting with 30-80% acetonitrile/water with 0.1% TFA

出典と根拠

ORDレコード
ord-5f1188499bc9499daeb916851c774116
出典データセット
uspto-grants-2010_04
特許番号
US07691887B2

反応ノート

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