Sodium hydride → 3-Iodo-1-((8-methyl-2-o-tolylquinolin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

HRID 2074494ノート

反応式

HRID 2074494 の反応式
[I:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[NH:4][N:3]=1.[H-].[Na+].Cl[CH2:15][C:16]1[C:17]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[CH3:33])=[N:18][C:19]2[C:24]([CH:25]=1)=[CH:23][CH:22]=[CH:21][C:20]=2[CH3:26]>CN(C=O)C>[I:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[N:4]([CH2:15][C:16]2[C:17]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[CH3:33])=[N:18][C:19]3[C:24]([CH:25]=2)=[CH:23][CH:22]=[CH:21][C:20]=3[CH3:26])[N:3]=1

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 575561733-(Chloromethyl)-8-methyl-2-o-tolylquinolineHCID 178508725HCID 178508725、化合物

生成物 1

HCID 452790493-Iodo-1-((8-methyl-2-o-tolylquinolin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

実験手順

Prepared according to Procedure I. A solution of 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (400 mg, 1.5 mmol) in DMF (5 mL) at 0° C. was treated with NaH (60%, 67.4 mg, 1.1 eq) for 30 min before addition of a solution of 3-(chloromethyl)-8-methyl-2-o-tolylquinoline (435 mg, 1 eq) in DMF (2 mL). The mixture was stirred at room temperature over night. The reaction mixture was partitioned between DCM (50 mL) and water (50 mL). The insoluble was filtered and washed with DCM and water. The organic layer from the filtrate was separated, dried over Na2SO4, concentrated and purified by column chromatography on silica gel (eluent: DCM/MeOH, 25/1) to provide a white solid [PI3Kδ IC50=6 nM]. 1H-NMR (DMSO-d6) δ 7.96 (s, 1H), 7.85 (s, 1H), 7.63 (d, J=8.2 Hz, 1H), 7.44 (d, J=7.0 Hz, 1H), 7.31 (t, J=7.1 Hz, 1H), 6.94-6.99 (m, 4H), 5.26 (s, 2H), 2.45 (s, 3H), 1.79 (s, 3H). Mass Spectrum (ESI) m/e=507 (M+1).

後処理

  1. customPrepared
  2. customThe reaction mixture was partitioned between DCM (50 mL) and water (50 mL)
  3. filtrationThe insoluble was filtered
  4. washwashed with DCM and water
  5. customThe organic layer from the filtrate was separated
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. custompurified by column chromatography on silica gel (eluent: DCM/MeOH, 25/1)
  9. customto provide a white solid [PI3Kδ IC50=6 nM]

出典と根拠

ORDレコード
ord-36b7ed7d2cff49518784c2fbab99681f
出典データセット
uspto-grants-2011_04
特許番号
US07919498B2

反応ノート

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