Methanesulfonyl chloride → HCID 59374982, 화합물

HRID 661937노트

반응식

HRID 661937 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.[CH3:36][S:37](Cl)(=[O:39])=[O:38]>C1COCC1>[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][NH:1][S:37]([CH3:36])(=[O:39])=[O:38])=[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

4

반응물 2

HCID 31297Methanesulfonyl chlorideHCID 59375043HCID 59375043, 화합물

생성물 1

HCID 59374982HCID 59374982, 화합물수율 20%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

A solution of 7-(aminomethyl)-4-(2-methyl-3-(1-oxoisoindolin-2-yl)phenyl)-9H-carbazole-1-carboxamide (Example 33-1, 60 mg, 0.065 mmol) and TEA (23 μL, 0.163 mmol) in THF (1.3 mL) was treated with methanesulfonyl chloride (5.6 μL, 0.072 mmol) and the mixture was stirred at rt overnight. The mixture was concentrated and purified by preparative HPLC. The appropriate effluent fractions were concentrated and partitioned between EtOAc and NaHCO3 (aq). The organic phase was dried and concentrated, and the residue was purified further by column chromatography (eluting with a gradient from 40:60 hexane-EtOAc to EtOAc) to provide 4-(2-methyl-3-(1-oxoisoindolin-2-yl)phenyl)-7-(methylsulfonamidomethyl)-9H-carbazole-1-carboxamide as an off-white solid (7 mg, 18%). 1H NMR (400 MHz, DMSO-d6) δ 11.57 (1H, s), 8.19 (1H, br. s.), 8.02 (1H, d, J=7.7 Hz), 7.81 (1H, d, J=7.7 Hz), 7.73 (1H, s), 7.69 (2H, d, J=3.7 Hz), 7.61-7.65 (1H, m), 7.54-7.61 (2H, m), 7.51 (2H, t, J=7.7 Hz), 7.35 (1H, dd, J=7.5, 1.1 Hz), 7.00-7.08 (2H, m), 6.93-6.99 (1H, m), 4.88-5.05 (2H, m), 4.26 (2H, d, J=5.9 Hz), 2.87 (3H, s), 1.84 (3H, s). Mass spectrum m/z 539.2 (M+H)+.

후처리

  1. concentrationThe mixture was concentrated
  2. custompurified by preparative HPLC
  3. concentrationThe appropriate effluent fractions were concentrated
  4. custompartitioned between EtOAc and NaHCO3 (aq)
  5. customThe organic phase was dried
  6. concentrationconcentrated
  7. customthe residue was purified further by column chromatography (
  8. washeluting with a gradient from 40:60 hexane-EtOAc to EtOAc)

출처 및 근거

ORD 기록
ord-3999f693c3b54128a7b7f300efbe4f24
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08084620B2

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