Potassium Carbonate → 5-Bromo-2-[4-({[2'-fluoro-4'-(methylsulfonyl)-4-biphenylyl]oxy}methyl)-1-piperidinyl]pyrimidine

HRID 423501Notes

Reaction equation

HRID 423501 reaction equation
Cl.[F:2][C:3]1[CH:8]=[C:7]([S:9]([CH3:12])(=[O:11])=[O:10])[CH:6]=[CH:5][C:4]=1[C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH:21]2[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]2)=[CH:15][CH:14]=1.Cl[C:28]1[N:33]=[CH:32][C:31]([Br:34])=[CH:30][N:29]=1.C([O-])([O-])=O.[K+].[K+]>CS(C)=O>[Br:34][C:31]1[CH:30]=[N:29][C:28]([N:24]2[CH2:25][CH2:26][CH:21]([CH2:20][O:19][C:16]3[CH:15]=[CH:14][C:13]([C:4]4[CH:5]=[CH:6][C:7]([S:9]([CH3:12])(=[O:11])=[O:10])=[CH:8][C:3]=4[F:2])=[CH:18][CH:17]=3)[CH2:22][CH2:23]2)=[N:33][CH:32]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 6066655-Bromo-2-chloropyrimidineHCID 666734284-({[2'-Fluoro-4'-(methylsulfonyl)-4-biphenylyl]oxy}methyl)piperidine hydrochloride

Product 1

HCID 249940305-Bromo-2-[4-({[2'-fluoro-4'-(methylsulfonyl)-4-biphenylyl]oxy}methyl)-1-piperidinyl]pyrimidineYield 91%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-({[2′-fluoro-4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)piperidine hydrochloride (Example 66, Step 1, 0.12 g, 0.30 mmol), 2-chloro-5-bromopyrimidine (89 mg, 0.45 mmol) and K2CO3 (0.13 g, 0.90 mmol) in DMSO (5 mL) was degassed, purged with N2 and heated at 100° C. overnight. The mixture was allowed to cool to ambient temperature, and was poured into water (50 mL) and extracted with EtOAc. The combined organic extract was washed with water and brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product as a yellow solid. The crude product was triturated with hot hexanes containing 1% of MeOH to give 0.142 g (91%) of the title compound as an off-white solid. 1H NMR (400 MHz, CDCl3): δ 8.29 (s, 2H), 7.80-7.70 (m, 2H), 7.65-7.55 (m, 1H), 7.50 (d, 2H, J=7.6 Hz), 6.99 (d, 2H, J=8.7 Hz), 4.85-4.75 (m, 2H), 3.88 (d, 2H, J=6.3 Hz), 3.09 (s, 3H), 3.00-2.90 (m, 2H), 2.20-2.05 (m, 1H), 2.00-1.90 (m, 2H), 1.45-1.30 (m, 2H); LRMS (ESI), m/z 520/522 (M+H).

Workup

  1. customwas degassed
  2. custompurged with N2
  3. temperatureto cool to ambient temperature
  4. additionwas poured into water (50 mL)
  5. extractionextracted with EtOAc
  6. extractionThe combined organic extract
  7. washwas washed with water and brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationthe filtrate was concentrated
  11. customto give the crude product as a yellow solid
  12. customThe crude product was triturated with hot hexanes containing 1% of MeOH

Sources & evidence

ORD record
ord-685a3b6ab1414e6aad8998d636c91eb1
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

Loading…