Sodium borohydride → 7-(1-Hydroxyethyl)-4-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-9H-pyrido[3,4-b]indole-1-carboxamide

HRID 2361367노트

반응식

HRID 2361367 반응식
[C:1]([C:4]1[CH:12]=[C:11]2[C:7]([C:8]3[C:16]([C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([N:23]5[C:32](=[O:33])[C:31]6[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=6)[N:25]=[CH:24]5)[C:18]=4[CH3:34])=[CH:15][N:14]=[C:13]([C:35]([NH2:37])=[O:36])[C:9]=3[NH:10]2)=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[BH4-].[Na+]>O1CCCC1.CO>[OH:3][CH:1]([C:4]1[CH:12]=[C:11]2[C:7]([C:8]3[C:16]([C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([N:23]5[C:32](=[O:33])[C:31]6[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=6)[N:25]=[CH:24]5)[C:18]=4[CH3:34])=[CH:15][N:14]=[C:13]([C:35]([NH2:37])=[O:36])[C:9]=3[NH:10]2)=[CH:6][CH:5]=1)[CH3:2]

참가 물질

5

반응물 2

HCID 4311764Sodium borohydrideHCID 679945647-Acetyl-4-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-9H-pyrido[3,4-b]indole-1-carboxamide

생성물 1

HCID 706519677-(1-Hydroxyethyl)-4-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-9H-pyrido[3,4-b]indole-1-carboxamide수율 23.9%

시약·촉매·용매 2

HCID 887Methanol용매HCID 8028Tetrahydrofuran용매

실험 절차

To a cloudy solution of 7-acetyl-4-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-9H-pyrido[3,4-b]indole-1-carboxamide (45 mg, 0.092 mmol) in tetrahydrofuran (4 mL) and methanol (12 mL) at 0° C. was added sodium borohydride (17.46 mg, 0.462 mmol) in one portion. The mixture was stirred at room temperature for 20 min and then the reaction was quenched with ice cold water (15 mL). The resulting mixture was extracted with ethyl acetate (3×30 mL). The combined extract was washed with brine (25 mL) and dried over anhydrous MgSO4. The organic solution was concentrated under vacuum, and the residue was purified by reverse phase HPLC. The correct fraction was concentrated under vacuum, basified with saturated NaHCO3 solution, and extracted with dichloromethane (3×35 mL). The combined extract was washed with brine (30 mL) and dried over anhydrous MgSO4. Removal of solvent under vacuum provided the desired product (10.9 mg, 0.022 mmol, 23.5% yield) as a white solid. LCMS (M+H)+=490.1. 1H NMR (500 MHz, DMSO-d6) (recognizable peaks for the major atropisomer) δ: 11.78 (s, 1H), 8.44 (s, 1H), 8.30 (s, 1H), 8.28 (dd, J1=8.0 Hz, J2=1.4 Hz, 1H), 8.25 (s, 1H), 8.24 (s, 1H), 7.30 (m, 1H), 7.12 (m, 1H), 5.25 (s, 1H), 4.85 (m, 1H), 1.82 (s, 3H),

후처리

  1. customthe reaction was quenched with ice cold water (15 mL)
  2. extractionThe resulting mixture was extracted with ethyl acetate (3×30 mL)
  3. extractionThe combined extract
  4. washwas washed with brine (25 mL)
  5. dry with materialdried over anhydrous MgSO4
  6. concentrationThe organic solution was concentrated under vacuum
  7. customthe residue was purified by reverse phase HPLC
  8. concentrationThe correct fraction was concentrated under vacuum
  9. extractionextracted with dichloromethane (3×35 mL)
  10. extractionThe combined extract
  11. washwas washed with brine (30 mL)
  12. dry with materialdried over anhydrous MgSO4
  13. customRemoval of solvent under vacuum

출처 및 근거

ORD 기록
ord-6b1ebaa5984f4292822fbb2c088b9919
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08685969B2

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