2-Methylsulfonyl-4-benzyloxy-pyrimidine → (1S,5R)-3-[3-({4-[(phenylmethyl)oxy]-2-pyrimidinyl}oxy)propyl]-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

HRID 19669Notes

Reaction equation

HRID 19669 reaction equation
[F:1][C:2]([F:20])([F:19])[C:3]1[CH:8]=[CH:7][C:6]([C@:9]23[CH2:14][C@H:13]2[CH2:12][N:11]([CH2:15][CH2:16][CH2:17][OH:18])[CH2:10]3)=[CH:5][CH:4]=1.CS([C:25]1[N:30]=[C:29]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH:28]=[CH:27][N:26]=1)(=O)=O>CN(C=O)C>[C:33]1([CH2:32][O:31][C:29]2[CH:28]=[CH:27][N:26]=[C:25]([O:18][CH2:17][CH2:16][CH2:15][N:11]3[CH2:12][C@H:13]4[C@:9]([C:6]5[CH:5]=[CH:4][C:3]([C:2]([F:19])([F:1])[F:20])=[CH:8][CH:7]=5)([CH2:14]4)[CH2:10]3)[N:30]=2)[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1

Participants

4

Reactant 2

HCID 113575332-Methylsulfonyl-4-benzyloxy-pyrimidineHCID 593375943-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}-1-propanol

Product 1

HCID 57856489(1S,5R)-3-[3-({4-[(phenylmethyl)oxy]-2-pyrimidinyl}oxy)propyl]-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexaneYield 72.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}-1-propanol (P11, 144 mg) in dry DMF (1.8 mL) NaH (60% in mineral oil, 24 mg) was added at 0° C. The mixture was stirred at this temperature for 10 min, then at room temperature for 15 min. A solution of 2-(methylsulfonyl)-4-[(phenylmethyl)oxy]pyrimidine (135 mg) in dry DMF (1.1 mL) was then added. The reaction mixture was stirred at room temperature for 5 hours, then hydrolysed with water and extracted with ethyl acetate. The organic phase was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by a silica SPE cartridge (5 g) eluting with dichloromethane/methanol from 100/0 to 98/2 to give the title compound as a colourless oil (171 mg).

Workup

  1. waitat room temperature for 15 min
  2. stirringThe reaction mixture was stirred at room temperature for 5 hours
  3. extractionhydrolysed with water and extracted with ethyl acetate
  4. washThe organic phase was washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by a silica SPE cartridge (5 g)
  8. washeluting with dichloromethane/methanol from 100/0 to 98/2

Sources & evidence

ORD record
ord-02dcb318d6b7438f8b6fdc5f271a3bc7
Source dataset
uspto-grants-2010_06
Patent number
US07745458B2

Reaction notes

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