Ammonium formate → 3-fluoro-5-[3-[[1-(2-hydroxyphenyl)cyclopropyl]amino]-2-oxo-1(2H)-pyrazinyl]-4-methyl-benzoic acid methyl ester

HRID 337091Notes

Reaction equation

HRID 337091 reaction equation
Br[C:2]1[N:3]=[C:4]([NH:21][C:22]2([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[O:31]CC3C=CC=CC=3)[CH2:24][CH2:23]2)[C:5](=[O:20])[N:6]([C:8]2[CH:9]=[C:10]([CH:15]=[C:16]([F:19])[C:17]=2[CH3:18])[C:11]([O:13][CH3:14])=[O:12])[CH:7]=1.C([O-])=O.[NH4+]>C(O)C.[Pd]>[F:19][C:16]1[CH:15]=[C:10]([CH:9]=[C:8]([N:6]2[CH:7]=[CH:2][N:3]=[C:4]([NH:21][C:22]3([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=4[OH:31])[CH2:24][CH2:23]3)[C:5]2=[O:20])[C:17]=1[CH3:18])[C:11]([O:13][CH3:14])=[O:12]

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 866615883-[5-bromo-2-oxo-3-[[1-[2-(phenylmethoxy)phenyl]cyclopropyl]amino]-1(2H)-pyrazinyl]-5-fluoro-4-methyl-benzoic acid, methyl ester

Product 1

HCID 666898943-fluoro-5-[3-[[1-(2-hydroxyphenyl)cyclopropyl]amino]-2-oxo-1(2H)-pyrazinyl]-4-methyl-benzoic acid methyl esterYield 94.6%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Conditions

Temperature
75 °C

Procedure

To 3-[5-bromo-2-oxo-3-[[1-[2-(phenylmethoxy)phenyl]cyclopropyl]amino]-1(2H)-pyrazinyl]-5-fluoro-4-methyl-benzoic acid, methyl ester (Example 259a, 9.2 g) in ethanol (400 mL) was added ammonium formate (14.04 g) and 10% Pd/C (1.693 g). The reaction was heated at 75° C. for 1 h, filtered through celite washing the celite with further warm ethanol (100 mL) followed by dichloromethane (2000 mL) and the combined filtrates were evaporated, diluted with dichloromethane (1000 mL) and washed with water, dried (MgSO4) and evaporated to give the subtitle compound (6.16 g).

Workup

  1. filtrationfiltered through celite
  2. washwashing the celite
  3. temperaturewith further warm ethanol (100 mL)
  4. customthe combined filtrates were evaporated
  5. additiondiluted with dichloromethane (1000 mL)
  6. washwashed with water
  7. dry with materialdried (MgSO4)
  8. customevaporated

Sources & evidence

ORD record
ord-49b4341036154bbc90a5b24564a8766a
Source dataset
uspto-grants-2014_11
Patent number
US08889692B2

Reaction notes

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