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

HRID 658492

反応式

HRID 658492 の反応式
[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

参加物

6

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 241Benzene溶媒HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-42cb988f1dd64c1da18e768779d9d0bc
出典データセット
uspto-grants-2011_12
特許番号
US08076488B2

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