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

HRID 2074494노트

반응식

HRID 2074494 반응식
[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

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 575561733-(Chloromethyl)-8-methyl-2-o-tolylquinolineHCID 178508725HCID 178508725, 화합물

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

실험 절차

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).

후처리

  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]

출처 및 근거

ORD 기록
ord-36b7ed7d2cff49518784c2fbab99681f
출처 데이터셋
uspto-grants-2011_04
특허 번호
US07919498B2

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