HCID 57937642, compound → HCID 68569926, compound

HRID 1435113Notes

Reaction equation

HRID 1435113 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@H:8]([O:10][C:11]1[CH:15]=[C:14]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][C:18]=2[N+:28]([O-])=O)[S:13][C:12]=1[C:31]([O:33][CH3:34])=[O:32])[CH3:9]>CCOC(C)=O.[Pt]>[NH2:28][C:18]1[CH:19]=[C:20]([O:23][C:24]([F:27])([F:26])[F:25])[CH:21]=[CH:22][C:17]=1[NH:16][C:14]1[S:13][C:12]([C:31]([O:33][CH3:34])=[O:32])=[C:11]([O:10][C@@H:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[Cl:1])[CH3:9])[CH:15]=1

Participants

4

Reactant 1

HCID 57937642HCID 57937642, compound

Product 1

HCID 68569926HCID 68569926, compoundYield 99.7%

Reagents, catalysts & solvents 2

HCID 23939PlatinumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

Methyl 3-{[(1R)-1-(2-chlorophenyl)ethyl]oxy}-5-({2-nitro-4-[(trifluoromethyl)oxy]phenyl}amino)-2-thiophenecarboxylate (3.5 g, 6.8 mmol) was dissolved in EtOAc (100 mL) with stirring. Sulfided platinum (5% weight on carbon, 1.32 g) was added, and the reaction was placed under 50 atm of H2. After 36 h the reaction was filtered through a Celite pad washing with EtOAc. The filtrate was concentrated to afford 3.3 g of methyl 5-({2-amino-4-[(trifluoromethyl)oxy]phenyl}amino)-3-{[(1R)-1-(2-chlorophenyl)ethyl]oxy}-2-thiophenecarboxylate which was immediately dissolved in trimethyl orthoformate (50 mL) with stirring. Pyridinium p-toluenesulfonate (0.26 g, 1.0 mmol) was added in a single portion. The reaction was stirred for 24 h. The volatiles were evaporated under reduced pressure and the residue was dissolved in CHCl3 (30 mL) and TFA (30 mL). The mixture was heated to 60° C. for 2 h. The volatiles were evaporated under reduced pressure and the residue was quenched by the addition of 7 N ammonia in MeOH (40 mL). The volatiles were evaporated under reduced pressure and the residue was partitioned between DCM (200 mL) and water (100 mL). The layers were separated, and the organics were washed with water (3×50 mL), dried over Na2SO4, filtered and evaporated under reduced pressure. The resulting solid was taken up as a suspension in ether/hexanes(1/9), filtered and washed with ether/hexanes(1/9) to afford 1.5 g (62%) of the title compound as a solid. MS (ESI): 359 [M+H]+.

Workup

  1. filtrationAfter 36 h the reaction was filtered through a Celite pad
  2. washwashing with EtOAc
  3. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-ad5801f0b38441d7b4d60f745afc1ba5
Source dataset
uspto-grants-2009_11
Patent number
US07615643B2

Reaction notes

Loading…