Cesium fluoride → HCID 86722491, compound

HRID 718877Notes

Reaction equation

HRID 718877 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[N:10][N:11]3[CH:16]=[C:15]4[C:17]5([CH2:27][C:28]6[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=6)[CH2:25][CH2:24][C:23](=[O:26])[CH2:22][CH:18]5[CH2:19][CH2:20][CH2:21][C:14]4=[CH:13][C:12]=23)=[CH:4][CH:3]=1.[F-].[Cs+].C[Si](C)(C)[C:38]([F:41])([F:40])[F:39].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>COCCOC>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]=[N:10][N:11]3[CH:16]=[C:15]4[C:17]5([CH2:27][C:28]6[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=6)[CH2:25][CH2:24][C:23]([C:38]([F:41])([F:40])[F:39])([OH:26])[CH2:22][CH:18]5[CH2:19][CH2:20][CH2:21][C:14]4=[CH:13][C:12]=23)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 25953Cesium fluorideHCID 552549(Trifluoromethyl)trimethylsilaneHCID 2724141Tetrabutylammonium FluorideHCID 86722490HCID 86722490, compound

Product 1

HCID 86722491HCID 86722491, compound

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
-10 °C

Procedure

rac-(4aR,13bS)-9-(4-Fluorophenyl)-13 b-(pyridin-2-ylmethyl)-4,4a,5,6,7,13 b-hexahydro-1H-benzo[3,4]cyclohepta[1,2-d][1,2,3]triazolo[1,5-a]pyridin-3 (2H)-one (157, R1=4-Fluorophenyl, R2=Pyridin-2-ylmethyl) (0.139 g, 0.316 mmol) was suspended in DME (3 mL) and CsF (0.029 g, 0.19 mmol) was added. The mixture was cooled to about −10° C. then trimethyl(trifluoromethyl)silane (0.093 mL, 0.63 mmol) was added. After stirring overnight, TBAF (1 M in THF) (0.316 mL, 0.316 mmol) was added and the mixture was allowed to warm to rt. The mixture was concentrated under reduced pressure then the residue was purified on silica gel (12 g) using a gradient of 10-85% EtOAc in heptane. Product fractions were combined and concentrated under reduced pressure and then triturated with EtOAc to provide rac-(3R,4aR,13bS)-9-(4-fluorophenyl)-13b-(pyridin-2-ylmethyl)-3-(trifluoromethyl)-2,3,4,4a,5,6,7,13b-octahydro-1H-benzo[3,4]cyclohepta[1,2-d][1,2,3]triazolo[1,5-a]pyridin-3-ol (158, R1=4-Fluorophenyl, R2=Pyridin-2-ylmethyl, R3=Trifluoromethyl) (0.031 g, 20%); LC/MS, method 2, Rt=2.45 min, MS m/z 511 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.39 (s, 1H), 8.34-8.29 (m, 1H), 8.11 (s, 1H), 8.08-8.02 (m, 2H), 7.40-7.30 (m, 3H), 7.06-7.00 (m, 1H), 6.52-6.47 (m, 1H), 5.97 (s, 1H), 3.67 (d, J=13.4 Hz, 1H), 3.56-3.42 (m, 1H), 3.27-3.15 (m, 2H), 2.22-2.07 (m, 2H), 2.07-1.67 (m, 7H), 1.55-1.38 (m, 1H), 1.30-1.20 (m, 1H).

Workup

  1. temperatureto warm to rt
  2. concentrationThe mixture was concentrated under reduced pressure
  3. customthe residue was purified on silica gel (12 g)
  4. concentrationconcentrated under reduced pressure
  5. customtriturated with EtOAc

Sources & evidence

ORD record
ord-1e58bc5620a64b2cafed3290dfbcc3c9
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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