Diisopropylethylamine → methyl 2-fluoro-5-[3-{[1-(2-hydroxyphenyl)cyclopropyl]amino}-2-oxopyrazin-1(2H)-yl]-4-methylbenzoate

HRID 2070819Notes

Reaction equation

HRID 2070819 reaction equation
C([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[C:15]1([NH:18][C:19]2[C:20](=[O:38])[N:21]([C:26]3[C:27]([CH3:37])=[CH:28][C:29]([F:36])=[C:30]([CH:35]=3)[C:31]([O:33][CH3:34])=[O:32])[CH:22]=[C:23](Br)[N:24]=2)[CH2:17][CH2:16]1)C1C=CC=CC=1.C([O-])=O.[NH4+].CCN(C(C)C)C(C)C>C(O)C.[Pd]>[F:36][C:29]1[CH:28]=[C:27]([CH3:37])[C:26]([N:21]2[CH:22]=[CH:23][N:24]=[C:19]([NH:18][C:15]3([C:10]4[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=4[OH:8])[CH2:17][CH2:16]3)[C:20]2=[O:38])=[CH:35][C:30]=1[C:31]([O:33][CH3:34])=[O:32]

Participants

6

Reactant 3

HCID 81531Diisopropylethylamine2×HCID 2723923Ammonium formate2×HCID 66689853methyl 5-[3-({1-[2-(benzyloxy)phenyl]cyclopropyl}amino)-5-bromo-2-oxopyrazin-1(2H)-yl]-2-fluoro-4-methylbenzoate

Product 1

HCID 66689715methyl 2-fluoro-5-[3-{[1-(2-hydroxyphenyl)cyclopropyl]amino}-2-oxopyrazin-1(2H)-yl]-4-methylbenzoateYield 65%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Conditions

Temperature
75 °C

Procedure

To methyl 5-[3-({1-[2-(benzyloxy)phenyl]cyclopropyl}amino)-5-bromo-2-oxopyrazin-1(2H)-yl]-2-fluoro-4-methylbenzoate (Example 318e, 2.310 g) in ethanol (30 mL) was added ammonium formate (3.53 g) and Pd/C (0.042 g). The reaction was heated at 75° C. for 3 h. Hunig's Base (3 mL) was added, and the reaction was heated at 90° C. for 4 h. Additional catalyst, ammonium formate and hunigs base were added, and the reaction was heated at 90° C. for 4 h. The reaction mixture was then filtered warm, through a fibre glass filter, washing through with 500 mL ethanol, followed by 500 mL DCM, followed by 500 mL 10% methanol/DCM. The DCM and MeOH/DCM filtrates were combined, evaporated, and the resulting residue partitioned between DCM and water. The organic layer was separated, dried (MgSO4), filtered, and evaporated to give the subtitle compound as a solid (1.063 g).

Workup

  1. temperaturethe reaction was heated at 90° C. for 4 h
  2. temperaturethe reaction was heated at 90° C. for 4 h
  3. filtrationThe reaction mixture was then filtered
  4. temperaturewarm, through a fibre glass
  5. filtrationfilter
  6. washwashing through with 500 mL ethanol
  7. customevaporated
  8. customthe resulting residue partitioned between DCM and water
  9. customThe organic layer was separated
  10. dry with materialdried (MgSO4)
  11. filtrationfiltered
  12. customevaporated

Sources & evidence

ORD record
ord-e4e9c220da484b05b6a4da9bca9b3428
Source dataset
uspto-grants-2012_10
Patent number
US08299246B2

Reaction notes

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