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

HRID 2074914Notes

Reaction equation

HRID 2074914 reaction equation
[F:1][C:2]([F:53])([F:52])[C:3]1[CH:4]=[C:5]([C:13]([CH3:51])([CH3:50])[C:14]([N:16]([C:18]2[CH:19]=[N:20][C:21]([N:31]3[C@H:40]([CH2:41][O:42][Si](C(C)(C)C)(C)C)[CH2:39][N:38]4[C@H:33]([CH2:34][O:35][CH2:36][CH2:37]4)[CH2:32]3)=[CH:22][C:23]=2[C:24]2[CH:25]=[N:26][CH:27]=[CH:28][C:29]=2[CH3:30])[CH3:17])=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.Cl>CO>[F:11][C:9]([F:10])([F:12])[C:7]1[CH:6]=[C:5]([C:13]([CH3:51])([CH3:50])[C:14]([N:16]([C:18]2[CH:19]=[N:20][C:21]([N:31]3[C@H:40]([CH2:41][OH:42])[CH2:39][N:38]4[C@H:33]([CH2:34][O:35][CH2:36][CH2:37]4)[CH2:32]3)=[CH:22][C:23]=2[C:24]2[CH:25]=[N:26][CH:27]=[CH:28][C:29]=2[CH3:30])[CH3:17])=[O:15])[CH:4]=[C:3]([C:2]([F:1])([F:53])[F:52])[CH:8]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 592158502-[3,5-bis(trifluoromethyl)phenyl]-N-{6'-[(7S,9aS)-7-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)hexahydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl]-4-methyl-3,4'-bipyridin-3'-yl}-N,2-dimethylpropanamide

Product 1

HCID 160638662-[3,5-Bis(trifluoromethyl)phenyl]-n{6'-[(7s,9as)-7-(hydroxymethyl)hexahydropyrazino[2,1-c][1,4]oxazin-8(1h)-yl]-4-methyl-3,4'-bipyridin-3'-yl}-n,2-dimethylpropanamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

2-[3,5-bis(trifluoromethyl)phenyl]-N-{6′-[(7S,9aS)-7-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)hexahydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl]-4-methyl-3,4′-bipyridin-3′-yl}-N,2-dimethylpropanamide (D53, 86 mg) was dissolved in dry MeOH (4 mL), cooled in an ice/salt bath to ˜0° C. before adding c.HCl solution. The mixture was stirred at ˜0° C. for 45 mins before allowing to warm up to R.T. and stirring for a further 2 hrs. Placed on a 5 g SCX column, washed with MeOH ×3, before eluting compound off with NH3 in MeOH. Solvent evaporated. Residue purified on a 5 g sek pak column eluting with Pent to EtOAc to 10% MeOH/EtOAc. Solvent evaporated to dryness in vacuo to afford a colourless gum of the title compound.

Workup

  1. additionbefore adding c
  2. temperatureto warm up to R.T.
  3. stirringstirring for a further 2 hrs
  4. washwashed with MeOH ×3
  5. washbefore eluting compound off with NH3 in MeOH
  6. customSolvent evaporated
  7. customResidue purified on a 5 g sek pak column
  8. washeluting with Pent to EtOAc to 10% MeOH/EtOAc
  9. customSolvent evaporated to dryness in vacuo

Sources & evidence

ORD record
ord-37e32643bdff44cf9bd7d9dcc85058df
Source dataset
uspto-grants-2011_04
Patent number
US07919491B2

Reaction notes

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