Sodium methanethiolate → HCID 86722485, compound

HRID 718868Notes

Reaction equation

HRID 718868 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)=[CH:19][CH:18]=3)[C:15]=2[CH:16]=1)[CH3:2].[CH3:33][S-:34].[Na+]>CN(C)C(=O)C>[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]([S:34][CH3:33])=[CH:19][CH:18]=3)[C:15]=2[CH:16]=1)[CH3:2]

Participants

4

Reactant 2

HCID 4378561Sodium methanethiolateHCID 86722395HCID 86722395, compound

Product 1

HCID 86722485HCID 86722485, compound

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

(3R,4aR,12bR)-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) (0.240 g, 0.538 mmol), sodium methanethiolate (0.188 g, 2.69 mmol) and N,N-dimethylacetamide (12 mL) were heated via microwave at about 90° C. for about 1 h. The reaction mixture was purified without manipulation in two portions by preparative reverse phase HPLC using a Hypersil HS C18 column (250 mm×21.2 mm, 8 μm particle size) with a gradient of 50-100% MeCN in 0.05 N aq. ammonium acetate pH 4.5 buffer. Product fractions were concentrated under reduced pressure then basified with sat. NaHCO3 then extracted with EtOAc. The organic solution was dried over MgSO4, filtered and concentrated under reduced pressure to yield (3R,4aR,12bR)-12b-ethyl-9-(4-(methylthio)phenyl)-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-(Methylthio)phenyl, R2=Ethyl, R3=Trifluoromethyl) (0.230 g, 90%); LC/MS, method 3, Rt=2.90 min, MS m/z 475 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.24 (d, J=1.3 Hz, 1H), 7.83 (s, 1H), 7.75-7.68 (m, 2H), 7.57 (s, 1H), 7.48-7.42 (m, 2H), 5.84 (s, 1H), 3.23-3.19 (m, 1H), 2.95-2.90 (m, 1H), 2.54 (s, 3H), 2.27-2.18 (m, 1H), 2.15-1.95 (m, 4H), 1.91-1.76 (m, 2H), 1.70-1.57 (m, 5H), 1.38-1.29 (m, 1H), 0.43 (t, J=7.3 Hz, 3H).

Workup

  1. customThe reaction mixture was purified without manipulation in two portions by preparative reverse phase HPLC
  2. concentrationProduct fractions were concentrated under reduced pressure
  3. extractionthen extracted with EtOAc
  4. dry with materialThe organic solution was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-6b26096f61fe4bb9bb68429c88f9b7d2
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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