3-Chloropropanesulphonyl chloride → HCID 86722365、化合物

HRID 718778ノート

反応式

HRID 718778 の反応式
[CH2:1]([O:8][C@@:9]1([C:36]([F:39])([F:38])[F:37])[CH2:33][C@H:13]2[CH2:14][CH2:15][CH2:16][C:17]3[C:18](=[CH:19][C:20]4[CH:21]=[N:22][N:23]([C:26]5[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=5)[C:24]=4[CH:25]=3)[C@:12]2([CH2:34][NH2:35])[CH2:11][CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[CH2:41][CH2:42][CH2:43][S:44](Cl)(=[O:46])=[O:45].[H-].[Na+]>C(Cl)Cl.CN(C=O)C>[CH2:1]([O:8][C@@:9]1([C:36]([F:38])([F:39])[F:37])[CH2:33][C@H:13]2[CH2:14][CH2:15][CH2:16][C:17]3[C:18](=[CH:19][C:20]4[CH:21]=[N:22][N:23]([C:26]5[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=5)[C:24]=4[CH:25]=3)[C@:12]2([CH2:34][N:35]2[CH2:41][CH2:42][CH2:43][S:44]2(=[O:46])=[O:45])[CH2:11][CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参加物

6

反応物 3

HCID 154103-Chloropropanesulphonyl chlorideHCID 24758Sodium hydrideHCID 86722363HCID 86722363、化合物

生成物 1

HCID 86722365HCID 86722365、化合物収率 64.2%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
50 °C

実験手順

A solution of ((3R,4aR,12bS)-3-(benzyloxy)-9-(4-fluorophenyl)-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazol-12b-yl)methanamine (34, R1=4-Fluorophenyl, R3=Trifluoromethyl, Rg=Benzyl) (82 mg, 0.153 mmol) in DCM (3 mL) was treated with TEA (0.021 mL, 0.153 mmol) and 3-chloro-propane-1-sulfonyl chloride (0.023 mL, 0.19 mmol) at rt under nitrogen for about 1 h. The organic layer was washed with 2N aq. HCl (2 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was dissolved in DMF (2 mL) and added dropwise to a suspension of sodium hydride (60 wt % in oil, 7.6 mg, 0.30 mmol) in DMF (1 mL). The reaction was heated at about 50° C. for 2 h and then cooled to rt and concentrate under reduced pressure. The residue was purified on silica gel (4 g) using a gradient of 0-30% EtOAc in DCM. Product fractions were combined and concentrated to yield 2-(((3R,4aR,12bS)-3-(benzyloxy)-9-(4-fluorophenyl)-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazol-12b-yl)methyl)isothiazolidine 1,1-dioxide (35, R1=4-Fluorophenyl, R3=Trifluoromethyl, Rg=Benzyl) (63 mg, 64%) as an oil. LC/MS, method 3, Rt=3.01 min, MS m/z 642 (M+H)+. The oil was used in step #2 without further purification.

後処理

  1. washThe organic layer was washed with 2N aq. HCl (2 mL)
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in DMF (2 mL)
  6. temperaturecooled to rt
  7. concentrationconcentrate under reduced pressure
  8. customThe residue was purified on silica gel (4 g)
  9. concentrationconcentrated

出典と根拠

ORDレコード
ord-81944e0ad9044c56ab04657efffbd84f
出典データセット
uspto-grants-2015_11
特許番号
US09193744B2

反応ノート

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