Cesium fluoride → HCID 86722484, compound

HRID 718867Notes

Reaction equation

HRID 718867 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[CH: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:7]=[CH:6][C:5]([C:8]2[N:9]=[CH: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:4][CH:3]=1

Participants

6

Reactant 4

HCID 25953Cesium fluorideHCID 552549(Trifluoromethyl)trimethylsilaneHCID 2724141Tetrabutylammonium FluorideHCID 86722482HCID 86722482, compound

Product 1

HCID 86722484HCID 86722484, compound

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
-10 °C

Procedure

rac-(4aR,13bS)-9-(4-fluorophenyl)-13b-(pyridin-2-ylmethyl)-4,4a,5,6,7,13 b-hexahydro-1H-benzo[3,4]cyclohepta[1,2-d]imidazo[1,5-a]pyridin-3 (2H)-one (149, R1=4-Fluorophenyl, R2=Pyridin-2-ylmethyl) (0.291 g, 0.662 mmol) was suspended in DME (7 mL) then CsF (0.060 g, 0.397 mmol) was added. The mixture was cooled to about −10° C. then trimethyl(trifluoromethyl)silane (0.185 g, 1.30 mmol) was added. After 15 min TBAF (1 M in THF) (0.695 mL, 0.695 mmol) was added and the mixture was allowed to warm to rt. The mixture was concentrated under reduced pressure then water (25 mL) was added to the material and the resulting solids collected by filtration. The material was purified on silica gel (12 g) using a gradient from 0-10% MeOH in DCM. Product fractions were combined and concentrated under reduced pressure to yield 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]imidazo[1,5-a]pyridin-3-ol (151, R1=4-Fluorophenyl, R2=Pyridin-2-ylmethyl, R3=Trifluoromethyl) (0.185 g, 55%); LC/MS, method 2, Rt=2.54 min, MS m/z 510 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.39-8.37 (m, 1H), 8.18 (s, 1H), 7.98-7.89 (m, 3H), 7.74 (s, 1H), 7.40-7.36 (m, 1H), 7.27-7.18 (m, 2H), 7.09-7.03 (m, 1H), 6.47 (d, J=7.8 Hz, 1H), 5.97 (s, 1H), 3.59 (d, J=13.2 Hz, 1H), 3.43-3.32 (m, 1H), 3.15 (d, J=13.4 Hz, 1H), 3.08-3.03 (m, 1H), 2.23-2.17 (m, 1H), 2.13-2.07 (m, 1H), 2.04-1.86 (m, 3H), 1.83-1.67 (m, 5H), 1.46-1.36 (m, 1H).

Workup

  1. temperatureto warm to rt
  2. concentrationThe mixture was concentrated under reduced pressure
  3. additionwater (25 mL) was added to the material
  4. filtrationthe resulting solids collected by filtration
  5. customThe material was purified on silica gel (12 g)
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-48cb0e3773924756a17fe6685614a3ec
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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