1,1'-Carbonyldiimidazole → 4-[3-fluoro-4-({[(1-methyl-1H-indazol-5-yl)amino]carbonyl}amino)phenoxy]-N-methylpyridine-2-carboxamide

HRID 658492

반응식

HRID 658492 반응식
[C:1]([N:8]1[CH:12]=[CH:11]N=C1)([N:3]1[CH:7]=[CH:6]N=C1)=[O:2].NC1C=[CH:29][C:17]([O:18][C:19]2[CH:24]=[CH:23][N:22]=[C:21]([C:25]([NH:27][CH3:28])=[O:26])[CH:20]=2)=[CH:16][C:15]=1[F:31].[CH3:32][N:33]1[C:41]2[C:36](=CC(N)=[CH:39][CH:40]=2)[CH:35]=[N:34]1>C1C=CC=CC=1.C(Cl)Cl>[F:31][C:15]1[CH:16]=[C:17]([CH:29]=[CH:11][C:12]=1[NH:8][C:1]([NH:3][C:7]1[CH:6]=[C:36]2[C:41](=[CH:40][CH:39]=1)[N:33]([CH3:32])[N:34]=[CH:35]2)=[O:2])[O:18][C:19]1[CH:24]=[CH:23][N:22]=[C:21]([C:25]([NH:27][CH3:28])=[O:26])[CH:20]=1

참가 물질

6

반응물 3

HCID 682631,1'-CarbonyldiimidazoleHCID 27680321-methyl-1H-indazol-5-amineHCID 468352194-(4-Amino-3-fluorophenoxy)-N-methylpyridine-2-carboxamide

생성물 1

HCID 104555834-[3-fluoro-4-({[(1-methyl-1H-indazol-5-yl)amino]carbonyl}amino)phenoxy]-N-methylpyridine-2-carboxamide수율 27%

시약·촉매·용매 2

HCID 241Benzene용매HCID 6344Dichloromethane용매

실험 절차

To a solution of 1,1′-carbonyldiimidazole (62 mg, 0.38 mmol) in benzene (2 mL) and CH2Cl2 (1 mL) was added 4-(4-amino-3-fluorophenoxy)-N-methylpyridine-2-carboxamide (100 mg, 0.38 mmol). The resulting solution was stirred at room temperature for 16 h, then was treated with 1-methyl-5-aminoindazole (56 mg, 0.38 mmol). The reaction continued to stir at room temperature for 18 h. The mixture was concentrated under reduced pressure and the residue was triturated with Et2O. The solid was collected by filtration, and then purified by preparative HPLC to afford 44 mg (27%) of the title product. 1H-NMR (DMSO-d6) δ 2.78 (d, J=4.8, 3H), 4.01 (s, 3H), 7.02-7.07 (m, 1H), 7.14-7.18 (m, 1H), 7.28-7.36 (m, 2H), 7.39 (d, J=2.9, 1H), 7.52-7.59 (m, 1H), 7.89-7.96 (m, 2H), 8.23 (t, J=9.0, 1H), 8.49 (d, J=4.9, 1H), 8.57-8.63 (m, 1H), 8.71-8.81 (m, 1H), 9.06 (s, 1H); MS LC-MS [M+H]+=435.1; mp 231-234° C.

후처리

  1. stirringto stir at room temperature for 18 h
  2. concentrationThe mixture was concentrated under reduced pressure
  3. customthe residue was triturated with Et2O
  4. filtrationThe solid was collected by filtration
  5. custompurified by preparative HPLC

출처 및 근거

ORD 기록
ord-42cb988f1dd64c1da18e768779d9d0bc
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08076488B2

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