Methanesulfonyl chloride → (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(6-(methylsulfonamido)-1-oxoisoindolin-2-yl)acetoxy)ethyl)pyridine 1-oxide

HRID 571180ノート

反応式

HRID 571180 の反応式
[NH2:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][N:7]([CH2:12][C:13]([O:15][C@H:16]([C:27]3[CH:32]=[CH:31][C:30]([O:33][CH:34]([F:36])[F:35])=[C:29]([O:37][CH2:38][CH:39]4[CH2:41][CH2:40]4)[CH:28]=3)[CH2:17][C:18]3[C:23]([Cl:24])=[CH:22][N+:21]([O-:25])=[CH:20][C:19]=3[Cl:26])=[O:14])[C:8]2=[O:11])=[CH:4][CH:3]=1.[CH3:42][S:43](Cl)(=[O:45])=[O:44]>C(Cl)Cl.N1C=CC=CC=1>[Cl:24][C:23]1[CH:22]=[N+:21]([O-:25])[CH:20]=[C:19]([Cl:26])[C:18]=1[CH2:17][C@@H:16]([C:27]1[CH:32]=[CH:31][C:30]([O:33][CH:34]([F:35])[F:36])=[C:29]([O:37][CH2:38][CH:39]2[CH2:40][CH2:41]2)[CH:28]=1)[O:15][C:13](=[O:14])[CH2:12][N:7]1[CH2:6][C:5]2[C:9](=[CH:10][C:2]([NH:1][S:43]([CH3:42])(=[O:45])=[O:44])=[CH:3][CH:4]=2)[C:8]1=[O:11]

参加物

5

反応物 2

HCID 31297Methanesulfonyl chlorideHCID 86681602(S)-4-(2-(2-(6-amino-1-oxoisoindolin-2-yl)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide

生成物 1

HCID 86681603(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(6-(methylsulfonamido)-1-oxoisoindolin-2-yl)acetoxy)ethyl)pyridine 1-oxide収率 75%

試薬・触媒・溶媒 2

HCID 1049Pyridine溶媒HCID 6344Dichloromethane溶媒2 回

実験手順

(S)-4-(2-(2-(6-amino-1-oxoisoindolin-2-yl)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (50 mg, 0.08 mmol) was dissolved in CH2Cl2 (2 ml) and pyridine (50 μl), then methanesulfonyl chloride was added (11 mg, 0.1 mmol) at 0° C. The mixture was stirred at RT for 2 hours, then diluted with CH2Cl2 (20 ml) and quenched with HCl 1N aqueous solution (30 ml). The two phases were separated, and the organic phase washed with HCl 1N aqueous solution (2×20 ml), dried over Na2SO4 and evaporated under vacuum. The crude was purified by preparative HPLC (Method 2) to yield 41 mg of the title compound. (Yield 75%). 1H NMR (400 MHz, acetone) δ ppm 8.71-8.92 (m, 1H), 8.22 (s, 2H), 7.73 (m, 1H), 7.59 (m, 2H), 7.15-7.30 (m, 2H), 7.05 (dd, J=8.38, 1.76 Hz, 1H), 6.93 (t, 1H, CHF2), 6.15 (dd, J=9.70, 4.85 Hz, 1H), 4.49 (s, 2H), 4.44 (d, J=3.53 Hz, 2H), 3.98 (d, J=7.06 Hz, 2H), 3.55 (dd, J=14.11, 9.26 Hz, 1H), 3.32 (dd, J=14.11, 4.85 Hz, 1H), 3.05 (s, 3H), 1.29 (m, 1H), 0.55-0.69 (m, 2H), 0.27-0.47 (m, 2H); MS/ESI+ 686.51 [MH]+.

後処理

  1. customquenched with HCl 1N aqueous solution (30 ml)
  2. customThe two phases were separated
  3. washthe organic phase washed with HCl 1N aqueous solution (2×20 ml)
  4. dry with materialdried over Na2SO4
  5. customevaporated under vacuum
  6. customThe crude was purified by preparative HPLC (Method 2)

出典と根拠

ORDレコード
ord-52d70e72555741ccb07abb36ec05dee3
出典データセット
uspto-grants-2015_05
特許番号
US09024027B2

反応ノート

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