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

HRID 908647Notes

Reaction equation

HRID 908647 reaction equation
[F:1][C:2]([F:47])([F:46])[O:3][C:4]1[CH:45]=[CH:44][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]([CH:41]3[CH2:43][CH2:42]3)=[CH:37][CH:36]=2)(=[O:34])=[O:33])=[O:11])=[CH:6][CH:5]=1.C([O-])=O.[NH4+]>C(O)C.CCCCCC.[C].[Pd]>[F:47][C:2]([F:1])([F:46])[O:3][C:4]1[CH:45]=[CH:44][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: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]([CH:41]3[CH2:43][CH2:42]3)=[CH:37][CH:36]=2)(=[O:34])=[O:33])=[O:11])=[CH:6][CH:5]=1

Participants

6

Reactant 2

HCID 2723923Ammonium formate3×HCID 59703751(R)-4-(7-chloro-5-trifluoromethyl-thiazolo[4,5-d]pyrimidin-2-yl)-1-(4-cyclopropyl-benzenesulfonyl)-piperazine-2-carboxylic acid 4-trifluoromethoxy-benzylamide

Product 1

HCID 59703742(R)-4-(5-trifluoromethyl-thiazolo[4,5-d]pyrimidin-2-yl)-1-(4-cyclopropyl-benzenesulfonyl)-piperazine-2-carboxylic acid 4-trifluoromethoxy-benzylamideYield 49.3%

Reagents, catalysts & solvents 3

HCID 178418390HCID 178418390, compoundCatalyst3×HCID 702EthanolSolvent2×HCID 8058HexaneSolvent

Procedure

To a mixed solution of the compound (66 mg) obtained in Step 5, ammonium formate (28 mg) and ethanol (1.3 ml) was added 10% palladium carbon (33 mg) with heating under reflux. The mixture was stirred at the same temperature for 10 min and ammonium formate (28 mg) and 10% palladium carbon (33 mg) were added and the mixture was stirred for 10 min. Ammonium formate (28 mg) and 10% palladium carbon (33 mg) were further added. The reaction mixture was allowed to return to room temperature, and diluted with ethanol. The mixture was filtered through celite, and the filtrate was concentrated under reduced pressure. The residue was partitioned by adding ethyl acetate and water. The organic layer was dried over anhydrous magnesium sulfate, filtrated, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:methanol=20:1), and the obtained crude product was suspended in hexane, collected by filtration, and dried to give the title compound (31 mg).

Workup

  1. temperaturewith heating
  2. temperatureunder reflux
  3. stirringthe mixture was stirred for 10 min
  4. customto return to room temperature
  5. filtrationThe mixture was filtered through celite
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe residue was partitioned
  8. additionby adding ethyl acetate and water
  9. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  10. filtrationfiltrated
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by silica gel column chromatography (chloroform:methanol=20:1)
  13. customthe obtained crude product
  14. filtrationcollected by filtration
  15. customdried

Sources & evidence

ORD record
ord-27a6c4bfd58040f188ffeda2e765b868
Source dataset
uspto-grants-2011_09
Patent number
US08017612B2

Reaction notes

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