Ammonium formate → (R)-1-(4-trifluoromethoxy-benzenesulfonyl)-4-(5-trifluoromethyl-thiazolo[4,5-d]pyrimidin-2-yl)-piperazine-2-carboxylic acid 4-difluoromethoxy-3-fluoro-benzylamide

HRID 908622Notes

Reaction equation

HRID 908622 reaction equation
[F:1][CH:2]([F:49])[O:3][C:4]1[CH:47]=[CH:46][C:7]([CH2:8][NH:9][C:10]([C@H:12]2[CH2:17][N:16]([C:18]3[S:19][C:20]4[C:25](Cl)=[N:24][C:23]([C:27]([F:30])([F:29])[F:28])=[N:22][C:21]=4[N:31]=3)[CH2:15][CH2:14][N:13]2[S:32]([C:35]2[CH:40]=[CH:39][C:38]([O:41][C:42]([F:45])([F:44])[F:43])=[CH:37][CH:36]=2)(=[O:34])=[O:33])=[O:11])=[CH:6][C:5]=1[F:48].C([O-])=O.[NH4+]>C(O)C.[C].[Pd]>[F:49][CH:2]([F:1])[O:3][C:4]1[CH:47]=[CH:46][C:7]([CH2:8][NH:9][C:10]([C@H:12]2[CH2:17][N:16]([C:18]3[S:19][C:20]4[CH:25]=[N:24][C:23]([C:27]([F:29])([F:30])[F:28])=[N:22][C:21]=4[N:31]=3)[CH2:15][CH2:14][N:13]2[S:32]([C:35]2[CH:36]=[CH:37][C:38]([O:41][C:42]([F:45])([F:44])[F:43])=[CH:39][CH:40]=2)(=[O:33])=[O:34])=[O:11])=[CH:6][C:5]=1[F:48]

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 59703768(R)-4-(7-chloro-5-trifluoromethyl-thiazolo[4,5-d]pyrimidin-2-yl)-1-(4-trifluoromethoxy-benzenesulfonyl)-piperazine-2-carboxylic acid 4-difluoromethoxy-3-fluoro-benzylamide

Product 1

HCID 59703769(R)-1-(4-trifluoromethoxy-benzenesulfonyl)-4-(5-trifluoromethyl-thiazolo[4,5-d]pyrimidin-2-yl)-piperazine-2-carboxylic acid 4-difluoromethoxy-3-fluoro-benzylamideYield 71.8%

Reagents, catalysts & solvents 2

HCID 178418390HCID 178418390, compoundCatalystHCID 702EthanolSolvent

Procedure

Under an argon atmosphere, to a solution of the compound (912 mg) obtained in Step 6 and ammonium formate (750 mg) in ethanol (18 ml) was added 10% palladium carbon (912 mg). After stirring under refluxing conditions for 1 hr, the catalyst was filtered off. The filtrate was concentrated under reduced pressure, and the residue was partitioned by adding ethyl acetate and water. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtrated, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:n-hexane=10:1-1:2) to give the title compound (625 mg).

Workup

  1. filtrationthe catalyst was filtered off
  2. concentrationThe filtrate was concentrated under reduced pressure
  3. customthe residue was partitioned
  4. additionby adding ethyl acetate and water
  5. washThe organic layer was washed with water
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltrated
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (ethyl acetate:n-hexane=10:1-1:2)

Sources & evidence

ORD record
ord-dd276cdf10be4be38ba260cc88c0002d
Source dataset
uspto-grants-2011_09
Patent number
US08017612B2

Reaction notes

Loading…