Morpholine → 4-{6-Iodo-3-[(morpholin-4-yl)carbonyl]indazol-1-yl}pyrimidin-2-amine

HRID 1398582

反応式

HRID 1398582 の反応式
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([I:17])[CH:15]=3)[C:10]([C:18]([OH:20])=O)=[N:9]2)[CH:5]=[CH:4][N:3]=1.S(Cl)(Cl)=O.[NH:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1>C(Cl)Cl.CN(C=O)C.C([O-])([O-])=O.[Na+].[Na+]>[I:17][C:14]1[CH:15]=[C:16]2[C:11]([C:10]([C:18]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)=[O:20])=[N:9][N:8]2[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH2:1])[N:7]=2)=[CH:12][CH:13]=1

参加物

7

反応物 3

HCID 8083MorpholineHCID 24386Thionyl ChlorideHCID 681816001-(2-Aminopyrimidin-4-yl)-6-iodoindazole-3-carboxylic acid

生成物 1

HCID 681816904-{6-Iodo-3-[(morpholin-4-yl)carbonyl]indazol-1-yl}pyrimidin-2-amine収率 76.8%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide触媒HCID 6344Dichloromethane溶媒3 回HCID 10340Sodium Carbonate溶媒

反応条件

温度
50 °C

実験手順

To a solution of 1-(2-aminopyrimidin-4-yl)-6-iodoindazole-3-carboxylic acid (3 g, 7.87 mmol)) in DCM (40 mL), was added thionyl chloride (6.85 ml, 94.46 mmol) followed by DMF (catalytic, 3 drops). The mixture was stirred at 50° C. for 1 hour. The reaction mixture was concentrated in vacuo and DCM added and the concentration repeated (×2). The crude acid chloride (assumed 7.87 mmol) was suspended in more DCM (30 mL) and morpholine (1.37 ml, 15.74 mmol) was added at 0 dropwise. The reaction was stirred at RT overnight. The reaction mixture was diluted with more DCM (25 ml) and 2M Na2CO3 added (35 ml). A pale brown precipitate was collected by filtration and washed with more DCM. The precipitate was slurried in water:acetonitrile (3:1, 10 ml) and the off-white solid collected by filtration and washed with more water:acetonitrile (3:1, 2×1 ml). The solid was then dried under vacuum to give the title compound (2.72 g, LC-MS purity=86%): 1H NMR (500 MHz, DMSO) delta 3.41-3.76 (6H, m), 3.85-3.97 (2H, m), 7.05 (1H, d, J=5.5 Hz), 7.18 (2H, s), 7.74 (1H, dd, J=8.4, 1.1 Hz), 7.80 (1H, d, J=8.4 Hz), 8.34 (1H, d, J=5.5 Hz), 9.33 (1H, s); LC-MS: m/z=+450.90 (M+H)+.

後処理

  1. concentrationThe reaction mixture was concentrated in vacuo and DCM
  2. additionadded
  3. concentrationthe concentration
  4. stirringThe reaction was stirred at RT overnight
  5. additionadded (35 ml)
  6. filtrationA pale brown precipitate was collected by filtration
  7. washwashed with more DCM
  8. filtrationthe off-white solid collected by filtration
  9. washwashed with more water:acetonitrile (3:1, 2×1 ml)
  10. customThe solid was then dried under vacuum

出典と根拠

ORDレコード
ord-956e8ec944a746819d547110704f1fe1
出典データセット
uspto-grants-2014_12
特許番号
US08901313B2

関連ノート

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