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

HRID 1398582

반응식

HRID 1398582 반응식
[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

참가 물질

7

반응물 3

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

생성물 1

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

시약·촉매·용매 3

HCID 6228Dimethylformamide촉매HCID 6344Dichloromethane용매3회HCID 10340Sodium Carbonate용매

반응 조건

온도
50 °C

실험 절차

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)+.

후처리

  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

출처 및 근거

ORD 기록
ord-956e8ec944a746819d547110704f1fe1
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08901313B2

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