Methanesulfonyl chloride → HCID 59374982、化合物

HRID 661937ノート

反応式

HRID 661937 の反応式
[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

参加物

4

反応物 2

HCID 31297Methanesulfonyl chlorideHCID 59375043HCID 59375043、化合物

生成物 1

HCID 59374982HCID 59374982、化合物収率 20%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

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)+.

後処理

  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)

出典と根拠

ORDレコード
ord-3999f693c3b54128a7b7f300efbe4f24
出典データセット
uspto-grants-2011_12
特許番号
US08084620B2

反応ノート

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