Pyridine → (2Rs,3rs)-3-(4-[4-cyanophenyl]thiazol-2-yl)-2-(2,4-difluorophenyl)-1-(1h-1,2,4-triazol-1-yl)-2-butyl dihydrogen phosphate

HRID 1006655Notes

Reaction equation

HRID 1006655 reaction equation
[P:1]([O:19][C:20]([C:42]1[CH:47]=[CH:46][C:45]([F:48])=[CH:44][C:43]=1[F:49])([CH:27]([C:29]1[S:30][CH:31]=[C:32]([C:34]2[CH:39]=[CH:38][C:37]([C:40]#[N:41])=[CH:36][CH:35]=2)[N:33]=1)[CH3:28])[CH2:21][N:22]1[CH:26]=[N:25][CH:24]=[N:23]1)([O:11]CC1C=CC=CC=1)([O:3]CC1C=CC=CC=1)=[O:2].Br[Si](C)(C)C.N1C=CC=CC=1.[OH-].[Na+]>C(Cl)Cl>[P:1]([OH:11])([OH:3])([O:19][C:20]([C:42]1[CH:47]=[CH:46][C:45]([F:48])=[CH:44][C:43]=1[F:49])([CH:27]([C:29]1[S:30][CH:31]=[C:32]([C:34]2[CH:39]=[CH:38][C:37]([C:40]#[N:41])=[CH:36][CH:35]=2)[N:33]=1)[CH3:28])[CH2:21][N:22]1[CH:26]=[N:25][CH:24]=[N:23]1)=[O:2]

Participants

6

Reactant 4

HCID 1049PyridineHCID 14798Sodium HydroxideHCID 76113BromotrimethylsilaneHCID 86610195Dibenzyl (2RS,3RS)-3-(4-[4-cyanophenyl]thiazol-2-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butyl phosphate

Product 1

HCID 18710284(2Rs,3rs)-3-(4-[4-cyanophenyl]thiazol-2-yl)-2-(2,4-difluorophenyl)-1-(1h-1,2,4-triazol-1-yl)-2-butyl dihydrogen phosphateYield 35.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of the compound of step (a) (310 mg, 0.44 mmol) in methylene chloride (5 ml) was cooled to 0° C. and then treated with bromotrimethylsilane (303 mg, 1.98 mmol) and pyridine (215 mg, 3.70 mmol). The resulting mixture was stirred at 0° C. for 3 hours and then quenched with water (1 ml) containing sodium hydroxide (115 mg, 2.87 mmol). A yellow precipitate was formed, which was isolated by filtration and then partitioned between dilute sulphuric acid and methylene chloride. The organic phase was washed with brine, dried (MgSO4) and the solvent evaporated to give the title compound as a pale yellow solid (80 mg, 35%).

Workup

  1. customquenched with water (1 ml)
  2. customA yellow precipitate was formed
  3. customwhich was isolated by filtration
  4. custompartitioned between dilute sulphuric acid and methylene chloride
  5. washThe organic phase was washed with brine
  6. dry with materialdried (MgSO4)
  7. customthe solvent evaporated

Sources & evidence

ORD record
ord-9542333ea1b54b1689f7a15bff3e2a8f
Source dataset
uspto-grants-2004_09
Patent number
US06790957B2

Reaction notes

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