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

HRID 2361366ノート

反応式

HRID 2361366 の反応式
[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].[CH3:38][Mg]Br>O1CCCC1>[OH:3][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)([CH3:38])[CH3:2]

参加物

4

反応物 2

HCID 679945647-Acetyl-4-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-9H-pyrido[3,4-b]indole-1-carboxamideHCID 178418573HCID 178418573、化合物2 回

生成物 1

HCID 706509827-(2-Hydroxypropan-2-yl)-4-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-9H-pyrido[3,4-b]indole-1-carboxamide収率 44.6%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a 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 (10 mL) at 0° C. was added methylmagnesium bromide (0.154 mL, 0.462 mmol). The mixture was stirred at room temperature for 30 min. Additional methylmagnesium bromide (0.100 mL, 0.300 mmol) was added at 0° C., and the mixture was stirred at room temperature for another 30 min. The reaction was quenched with water (10 mL) and the 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 ethyl acetate (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 (20.9 mg, 0.041 mmol, 44.1% yield) as a pale yellow solid. LCMS (M+H)+=504.0. 1H NMR (500 MHz, DMSO-d6) (recognizable peaks for the major atropisomer) δ: 11.74 (s, 1H), 8.44 (s, 1H), 8.23 (s, 1H), 8.30 (s, 1H), 7.98 (m, 1H), 7.92 (m, 1H), 7.80 (m, 1H), 7.75 (m, 1H), 7.58 (m, 1H), 7.24 (m, 1H), 5.12 (s, 1H), 1.83 (s, 3H), 1.50 (s, 6H).

後処理

  1. stirringthe mixture was stirred at room temperature for another 30 min
  2. customThe reaction was quenched with water (10 mL)
  3. extractionthe mixture was extracted with ethyl acetate (3×30 mL)
  4. extractionThe combined extract
  5. washwas washed with brine (25 mL)
  6. dry with materialdried over anhydrous MgSO4
  7. concentrationThe organic solution was concentrated under vacuum
  8. customthe residue was purified by reverse phase HPLC
  9. concentrationThe correct fraction was concentrated under vacuum
  10. extractionextracted with ethyl acetate (3×35 mL)
  11. extractionThe combined extract
  12. washwas washed with brine (30 mL)
  13. dry with materialdried over anhydrous MgSO4
  14. customRemoval of solvent under vacuum

出典と根拠

ORDレコード
ord-dd54aad794ca4c08905f65f03d319c12
出典データセット
uspto-grants-2014_04
特許番号
US08685969B2

反応ノート

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