3-Chloropropanesulphonyl chloride → HCID 86722365, compound

HRID 718778Notes

Reaction equation

HRID 718778 reaction equation
[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

Participants

6

Reactant 3

HCID 154103-Chloropropanesulphonyl chlorideHCID 24758Sodium hydrideHCID 86722363HCID 86722363, compound

Product 1

HCID 86722365HCID 86722365, compoundYield 64.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-81944e0ad9044c56ab04657efffbd84f
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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