Hydrochloric Acid → HCID 59215785, compound

HRID 421288Notes

Reaction equation

HRID 421288 reaction equation
CC([Si](C)(C)[O:6][CH2:7][C@@H:8]1[CH2:13][N:12]2[CH2:14][CH2:15][CH2:16][C@H:11]2[CH2:10][NH:9]1)(C)C.[F:19][C:20]([F:54])([F:53])[C:21]1[CH:22]=[C:23]([C:31]([CH3:52])([CH3:51])[C:32]([N:34]([C:36]2[CH:37]=[N:38][C:39](Cl)=[CH:40][C:41]=2[C:42]2[CH:47]=[CH:46][C:45]([F:48])=[CH:44][C:43]=2[CH3:49])[CH3:35])=[O:33])[CH:24]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:26]=1.[OH-].[Na+].Cl>C1(C)C=CC=CC=1.[Cl-].C([N+](C)(C)C)CCCCCCCCCCCCCCC.CO>[F:30][C:27]([F:28])([F:29])[C:25]1[CH:24]=[C:23]([C:31]([CH3:52])([CH3:51])[C:32]([N:34]([C:36]2[CH:37]=[N:38][C:39]([N:9]3[C@H:8]([CH2:7][OH:6])[CH2:13][N:12]4[CH2:14][CH2:15][CH2:16][C@H:11]4[CH2:10]3)=[CH:40][C:41]=2[C:42]2[CH:47]=[CH:46][C:45]([F:48])=[CH:44][C:43]=2[CH3:49])[CH3:35])=[O:33])[CH:22]=[C:21]([C:20]([F:54])([F:19])[F:53])[CH:26]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 235027842-(3,5-Bis(trifluoromethyl)phenyl)-N-(6-chloro-4-(4-fluoro-2-methylphenyl)pyrid-3-yl)-N,2-dimethylpropanamideHCID 59215853HCID 59215853, compound

Product 1

HCID 59215785HCID 59215785, compoundYield 47.7%

Reagents, catalysts & solvents 3

HCID 8154Hexadecyltrimethylammonium chlorideCatalystHCID 887MethanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of (3S,8aS)-3-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)octahydropyrrolo[1,2-a]pyrazine (D82, 157 mg, 0.58 mmol) in 2.5 mL of toluene were added 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide [WO 2005/002577] (238 mg, 0.45 mmol) (t-Bu3P)2Pd (46 mg, 0.09 mmol), a 25% aqueous solution of cetyltrimethylammonium chloride (26 μL), and, at last, 50% aqueous NaOH (54 μL). The reaction deoxygenated by freeze-pump-thaw cycles and then heated to 90° C. for 7 h. The reaction was checked by UPLC/MS, showing the expected product peak at 0.84 min, with m/z=767 (M+1) and 384 ((M+2)/2). The solution was diluted with EtOAc, washed with sat. NaHCO3 and brine. The sample was purified by flash chromatography (silica, cyclohexane:EtOAc 90:10 to 0:100). Isolated 251 mg of O-TBDMS protected intermediate. The intermediate was dissolved in 11 mL of MeOH and 0.55 mL of conc. HCl were added. The reaction was left at room temperature for 1 h. The product was isolated by SCX cartridge. Isolated 140 mg of the title compound.

Workup

  1. customThe reaction deoxygenated by freeze-pump-thaw cycles
  2. customat 0.84 min
  3. additionThe solution was diluted with EtOAc
  4. washwashed with sat. NaHCO3 and brine
  5. customThe sample was purified by flash chromatography (silica, cyclohexane:EtOAc 90:10 to 0:100)
  6. customIsolated 251 mg of O-TBDMS protected intermediate
  7. customThe product was isolated by SCX cartridge

Sources & evidence

ORD record
ord-edefcdc948214853b7b547c0e8ef8a69
Source dataset
uspto-grants-2012_01
Patent number
US08097618B2

Reaction notes

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