Chlorosulfamic acid → HCID 74220988, compound

HRID 718870Notes

Reaction equation

HRID 718870 reaction equation
[CH2:1]([C@:3]12[CH2:27][CH2:26][C@:25]([C:29]([F:32])([F:31])[F:30])([OH:28])[CH2:24][C@@H:4]1[CH2:5][CH2:6][CH2:7][C:8]1[C:9]2=[CH:10][C:11]2[CH:12]=[N:13][N:14]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[C:15]=2[CH:16]=1)[CH3:2].[S:33](Cl)(=[O:36])(=[O:35])[NH2:34]>CN(C)C(=O)C>[S:33](=[O:36])(=[O:35])([O:28][C@:25]1([C:29]([F:32])([F:31])[F:30])[CH2:24][C@@H:4]2[CH2:5][CH2:6][CH2:7][C:8]3[C:9](=[CH:10][C:11]4[CH:12]=[N:13][N:14]([C:17]5[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=5)[C:15]=4[CH:16]=3)[C@@:3]2([CH2:1][CH3:2])[CH2:27][CH2:26]1)[NH2:34]

Participants

4

Reactant 2

HCID 24499Chlorosulfamic acid2×HCID 86722486HCID 86722486, compound

Product 1

HCID 74220988HCID 74220988, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

(3S,4aS,12bS)-12b-Ethyl-9-(4-fluorophenyl)-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazol-3-ol (11, R1=4-Fluorophenyl, R2=Ethyl, R3=Trifluoromethyl) (0.125 g, 0.280 mmol) in N,N-dimethylacetamide (3 mL) was stirred and treated with sulfamoyl chloride (0.105 g, 0.91 mmol). After about 3 h sulfamoyl chloride (0.080 g, 0.69 mmol) was added and the mixture was stirred for about 14 h at rt. The reaction mixture was purified without manipulation in one portion by preparative reverse phase HPLC using a Hypersil HS C18 column (250 mm×21.2 mm, 8 um particle size) with a gradient of 25-100% MeCN in 0.05 N aq. ammonium acetate pH 4.5 buffer. Product fractions were concentrated under reduced pressure then diluted with water (15 mL). The solids were collected by filtration then washed with water (5 mL) and dried to yield (3S,4aS,12bS)-12b-ethyl-9-(4-fluorophenyl)-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazol-3-yl sulfamate (109 mg, 74%); LC/MS, method 2, Rt=2.86 min, MS m/z 526 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.26 (d, J=0.8 Hz, 1H), 8.02 (s, 2H), 7.86 (s, 1H), 7.81-7.78 (m, 2H), 7.57 (s, 1H), 7.45-7.37 (m, 2H), 3.23-3.18 (m, 2H), 2.98-2.92 (m, 1H), 2.45-2.18 (m, 4H), 2.16-1.95 (m, 3H), 1.94-1.61 (m, 4H), 1.42-1.27 (m, 1H), 0.43 (t, J=7.3 Hz, 3H).

Workup

  1. customThe reaction mixture was purified without manipulation in one portion by preparative reverse phase HPLC
  2. concentrationProduct fractions were concentrated under reduced pressure
  3. additionthen diluted with water (15 mL)
  4. filtrationThe solids were collected by filtration
  5. washthen washed with water (5 mL)
  6. customdried

Sources & evidence

ORD record
ord-4e18afb97a994217acf3f10add920536
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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