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 639748노트

반응식

HRID 639748 반응식
[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

참가 물질

5

반응물 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

생성물 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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-5f1188499bc9499daeb916851c774116
출처 데이터셋
uspto-grants-2010_04
특허 번호
US07691887B2

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