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

HRID 1398600ノート

反応式

HRID 1398600 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(=O)([O-])[O-].[Na+].[Na+]>C(Cl)Cl.CN(C=O)C>[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 4

HCID 8083MorpholineHCID 10340Sodium CarbonateHCID 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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide触媒HCID 6344Dichloromethane溶媒2 回

反応条件

温度
50 °C

実験手順

To a solution of 1-(2-aminopyrimidin-4-yl)-6-iodo-1H-indazole-3-carboxylic acid (3.00 g, 7.87 mmol) in dry DCM (40 mL) was introduced thionyl chloride (6.85 mL, 94.46 mmol) and DMF (3 drops, cat.). The reaction mixture was warmed to 50° C. for 1 hr. After cooling to RT, the reaction mixture was concentrated in vacuo. The residue was re-dissolved in dry DCM (20 mL) and concentrated in vacuo (twice). After suspending the residue in dry DCM (30 mL), the solution was cooled to 0° C. under an atmosphere of nitrogen, and morpholine (1.37 mL, 15.74 mmol) added dropwise. The reaction mixture was warmed to RT for 16 hr. Following dilution with DCM (25 mL), 2M aqueous sodium carbonate (35 mL) was introduced. The resulting precipitate was collected by filtration and washed on the filter with DCM (5 mL) and dried. After suspension of the precipitate in 3:1 water/acetonitrile (10 mL), the slurry was collected by filtration and washed on the filter with further 3:1 water/acetonitrile (2×1 mL washes). The filter cake was dried under vacuum to furnish the title compound as an off-white solid: 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. temperatureAfter cooling to RT
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. dissolutionThe residue was re-dissolved in dry DCM (20 mL)
  4. concentrationconcentrated in vacuo (twice)
  5. temperaturethe solution was cooled to 0° C. under an atmosphere of nitrogen
  6. temperatureThe reaction mixture was warmed to RT for 16 hr
  7. additionwas introduced
  8. filtrationThe resulting precipitate was collected by filtration
  9. washwashed on the
  10. filtrationfilter with DCM (5 mL)
  11. customdried
  12. additionAfter suspension of the precipitate in 3:1 water/acetonitrile (10 mL)
  13. filtrationthe slurry was collected by filtration
  14. washwashed on the
  15. filtrationfilter with further 3:1 water/acetonitrile (2×1 mL washes)
  16. customThe filter cake was dried under vacuum

出典と根拠

ORDレコード
ord-f2713e1edab34368a6bd4482ecf728b6
出典データセット
uspto-grants-2014_12
特許番号
US08901313B2

反応ノート

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