Chloride → 2-[3,5-Bis(trifluoromethyl)phenyl]-n{6-fluoro-6'-[(7s,9as)-7-(hydroxymethyl)hexahydropyrazino[2,1-c][1,4]oxazin-8(1h)-yl]-2-methyl-3,4'-bipyridin-3'-yl}-n,2-dimethylpropanamide

HRID 2245485Notes

Reaction equation

HRID 2245485 reaction equation
[F:1][C:2]([F:36])([F:35])[C:3]1[CH:4]=[C:5]([C:13]([CH3:34])([CH3:33])[C:14]([N:16]([C:18]2[CH:19]=[N:20][C:21](Cl)=[CH:22][C:23]=2[C:24]2[C:25]([CH3:31])=[N:26][C:27]([F:30])=[CH:28][CH:29]=2)[CH3:17])=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.CC([Si](C)(C)[O:42][CH2:43][C@@H:44]1[CH2:53][N:52]2[C@H:47]([CH2:48][O:49][CH2:50][CH2:51]2)[CH2:46][NH:45]1)(C)C.[Cl-].[OH-].[Na+]>C1(C)C=CC=CC=1>[F:1][C:2]([F:36])([F:35])[C:3]1[CH:4]=[C:5]([C:13]([CH3:34])([CH3:33])[C:14]([N:16]([C:18]2[CH:19]=[N:20][C:21]([N:45]3[C@H:44]([CH2:43][OH:42])[CH2:53][N:52]4[C@H:47]([CH2:48][O:49][CH2:50][CH2:51]4)[CH2:46]3)=[CH:22][C:23]=2[C:24]2[C:25]([CH3:31])=[N:26][C:27]([F:30])=[CH:28][CH:29]=2)[CH3:17])=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

6

Reactant 4

HCID 312ChlorideHCID 14798Sodium HydroxideHCID 59215768(7S,9AS)-7-(((tert-butyldimethylsilyl)oxy)methyl)octahydropyrazino[2,1-c][1,4]oxazineHCID 592158222-[3,5-bis(trifluoromethyl)phenyl]-N-(6'-chloro-6-fluoro-2-methyl-3,4'-bipyridin-3'-yl)-N,2-dimethylpropanamide

Product 1

HCID 160639112-[3,5-Bis(trifluoromethyl)phenyl]-n{6-fluoro-6'-[(7s,9as)-7-(hydroxymethyl)hexahydropyrazino[2,1-c][1,4]oxazin-8(1h)-yl]-2-methyl-3,4'-bipyridin-3'-yl}-n,2-dimethylpropanamide

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

2-[3,5-bis(trifluoromethyl)phenyl]-N-(6′-chloro-6-fluoro-2-methyl-3,4′-bipyridin-3′-yl) -N,2-dimethylpropanamide (D54, 53.5 mg, 0.1 mmol), (7S,9aS)-7-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)octahydropyrazino[2,1-c][1,4]oxazine (D51, 37 mg, 0.13 mmol) were dissolved in toluene (1.5 mL). Bis tritertbutylphosphine palladium (13 mg, 0.026 mmol), followed by hexadecyltrimethylammoium chloride (10 μL, 25% aq sol), and finally sodium hydroxide solution (0.13 mL, 50% aq sol). The mixture was degassed for 5 minutes before heating at 90° C. for 4.5 hours. Cooled to R.T., diluted with EtOAc, washed with sat. NaHCO3 solution, dried (MgSO4).

Workup

  1. customThe mixture was degassed for 5 minutes
  2. temperatureCooled to R.T.
  3. additiondiluted with EtOAc
  4. washwashed with sat. NaHCO3 solution
  5. dry with materialdried (MgSO4)

Sources & evidence

ORD record
ord-fc9b8ea4790b4ace9ede1df170d930a5
Source dataset
uspto-grants-2010_03
Patent number
US07683056B2

Reaction notes

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