Sodium hydride → HCID 59375166, 화합물

HRID 661938노트

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HRID 661938 반응식
[NH2:1][CH2:2][C:3]1[CH:15]=[C:14]2[C:6]([C:7]3[C:8]([C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([N:25]5[CH2:33][C:32]6[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=6)[C:26]5=[O:34])[C:20]=4[CH3:35])=[CH:9][CH:10]=[C:11]([C:16]([NH2:18])=[O:17])[C:12]=3[NH:13]2)=[CH:5][CH:4]=1.CCN(C(C)C)C(C)C.Br[CH2:46][CH2:47][CH2:48][C:49](Cl)=[O:50].[H-].[Na+]>C1COCC1.C(Cl)Cl.CCOC(C)=O.O>[CH3:35][C:20]1[C:21]([N:25]2[CH2:33][C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[C:26]2=[O:34])=[CH:22][CH:23]=[CH:24][C:19]=1[C:8]1[C:7]2[C:6]3[C:14](=[CH:15][C:3]([CH2:2][N:1]4[CH2:46][CH2:47][CH2:48][C:49]4=[O:50])=[CH:4][CH:5]=3)[NH:13][C:12]=2[C:11]([C:16]([NH2:18])=[O:17])=[CH:10][CH:9]=1

참가 물질

9

반응물 4

HCID 24758Sodium hydrideHCID 702254-Bromobutyryl chlorideHCID 81531DiisopropylethylamineHCID 59375043HCID 59375043, 화합물

생성물 1

HCID 59375166HCID 59375166, 화합물수율 4.3%

시약·촉매·용매 4

HCID 962Water용매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

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온도
50 °C

실험 절차

A solution of 7-(aminomethyl)-4-(2-methyl-3-(1-oxoisoindolin-2-yl)phenyl)-9H-carbazole-1-carboxamide (Example 33-1, 80 mg, 0.087 mmol) in THF (3 mL) was treated with DIEA (0.030 mL, 0.174 mmol) and a solution of 4-bromobutanoyl chloride (10 μL, 0.087 mmol) in DCM (1 mL) and the mixture was stirred at rt for 35 min. The reaction mixture was diluted with EtOAc, washed with NaHCO3 (aq) and brine, and dried and concentrated. The residue was dissolved in THF (6 mL) and treated with sodium hydride (60% oil dispersion, 24.32 mg, 0.608 mmol). The resulting mixture was stirred at 50° C. for 2 h, then was diluted with water and extracted with EtOAc. The organic phase was dried and concentrated, and the residue was purified by preparative HPLC to provide 4-(2-methyl-3-(1-oxoisoindolin-2-yl)phenyl)-7-((2-oxopyrrolidin-1-yl)methyl)-9H-carbazole-1-carboxamide as a white solid (2 mg, 3%). 1H NMR (400 MHz, DMSO-d6) δ 11.44 (1H, s), 8.11 (1H, br. s.), 7.95 (1H, d, J=7.9 Hz), 7.73 (1H, d, J=7.5 Hz), 7.62 (2H, d, J=3.7 Hz), 7.46-7.57 (3H, m), 7.42 (2H, t, J=7.7 Hz), 7.23-7.29 (1H, m), 6.90-6.99 (2H, m), 6.74 (1H, dd, J=8.1, 1.5 Hz), 4.79-5.00 (2H, m), 4.25-4.51 (2H, m), 3.11-3.22 (2H, m), 2.19-2.29 (2H, m), 1.80-1.93 (2H, m), 1.77 (3H, s). Mass spectrum m/z 529.2 (M+H)+.

후처리

  1. washwashed with NaHCO3 (aq) and brine
  2. customdried
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in THF (6 mL)
  5. extractionextracted with EtOAc
  6. customThe organic phase was dried
  7. concentrationconcentrated
  8. customthe residue was purified by preparative HPLC

출처 및 근거

ORD 기록
ord-743ef6f9c8644eb0b592cf31e1441f8e
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08084620B2

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