Potassium Carbonate → methyl 5-[(3-{[2-fluoro-1-(fluoromethyl)ethyl]oxy}-5-{[(1-methyl-1H-pyrazol-3-yl)amino]carbonyl}phenyl)oxy]pyrazine-2-carboxylate

HRID 1175888Notes

Reaction equation

HRID 1175888 reaction equation
[F:1][CH2:2][CH:3]([O:6][C:7]1[CH:8]=[C:9]([CH:19]=[C:20]([OH:22])[CH:21]=1)[C:10]([NH:12][C:13]1[CH:17]=[CH:16][N:15]([CH3:18])[N:14]=1)=[O:11])[CH2:4][F:5].Cl[C:24]1[N:25]=[CH:26][C:27]([C:30]([O:32][CH3:33])=[O:31])=[N:28][CH:29]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[F:5][CH2:4][CH:3]([O:6][C:7]1[CH:21]=[C:20]([O:22][C:24]2[N:25]=[CH:26][C:27]([C:30]([O:32][CH3:33])=[O:31])=[N:28][CH:29]=2)[CH:19]=[C:9]([C:10]([NH:12][C:13]2[CH:17]=[CH:16][N:15]([CH3:18])[N:14]=2)=[O:11])[CH:8]=1)[CH2:2][F:1]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 406081Methyl 5-chloropyrazine-2-carboxylateHCID 591271643-{[2-fluoro-1-(fluoromethyl)ethyl]oxy}-5-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)benzamide

Product 1

HCID 59127106methyl 5-[(3-{[2-fluoro-1-(fluoromethyl)ethyl]oxy}-5-{[(1-methyl-1H-pyrazol-3-yl)amino]carbonyl}phenyl)oxy]pyrazine-2-carboxylateYield 90.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 3-{[2-fluoro-1-(fluoromethyl)ethyl]oxy}-5-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)benzamide (250 mg, 0.8 mmol), methyl 5-chloropyrazine-2-carboxylate (208 mg, 1.20 mmol) and potassium carbonate (222 mg, 1.61 mmol) in acetonitrile (5 mL) was stirred in a ‘Biotage initiator Microwave’ at 120° C. for 3 hours. The solvent was removed in vacuo and the residue dissolved in ethyl acetate (50 mL) and water (50 mL), the organic layer washed with brine (50 mL), dried (MgSO4), filtered and the solvent removed in vacuo to give a yellow oil which was chromatographed on silica, eluting with 0-100% ethyl acetate in isohexane, to give the desired compound (0.325 g). 1H NMR δ (CDCl3): 3.71 (s, 3H), 3.96 (s, 3H), 4.56 (m, 2H), 4.68 (m, 3H), 6.73 (s, 1H), 6.95 (s, 1H), 7.22 (s, 1H), 7.27 (s, 1H), 7.36 (s, 1H), 8.46 (s, 1H), 8.67 (s, 1H), 8.67 (s, 1H); m/z 448 (M+H)+

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthe residue dissolved in ethyl acetate (50 mL)
  3. washwater (50 mL), the organic layer washed with brine (50 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customthe solvent removed in vacuo
  7. customto give a yellow oil which
  8. customwas chromatographed on silica
  9. washeluting with 0-100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-cb9c70044e314c68a77a948ba263d471
Source dataset
uspto-grants-2010_11
Patent number
US07842694B2

Reaction notes

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