Potassium Carbonate → HCID 11186126, compound

HRID 917709Notes

Reaction equation

HRID 917709 reaction equation
[F:1][C:2]1[CH:21]=[C:20]([C:22]#[C:23][Si](C)(C)C)[CH:19]=[CH:18][C:3]=1[NH:4][C:5]1[C:6]([C:12]([NH:14][CH2:15][CH2:16][OH:17])=[O:13])=[CH:7][NH:8][C:9](=[O:11])[CH:10]=1.C([O-])([O-])=O.[K+].[K+]>CO.C1COCC1>[C:22]([C:20]1[CH:19]=[CH:18][C:3]([NH:4][C:5]2[C:6]([C:12]([NH:14][CH2:15][CH2:16][OH:17])=[O:13])=[CH:7][NH:8][C:9](=[O:11])[CH:10]=2)=[C:2]([F:1])[CH:21]=1)#[CH:23]

Participants

5

Reactant 2

HCID 11430Potassium CarbonateHCID 58962863HCID 58962863, compound

Product 1

HCID 11186126HCID 11186126, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

4-{2-Fluoro-4-[(trimethylsilyl)ethynyl]anilino}-N-(2-hydroxyethyl)-6-oxo-1,6-dihydro-3-pyridinecarboxamide (195 mg, 0.50 mmol) was dissolved/suspended in a mixture of MeOH (30 mL) and THF (20 mL) to which was added solid K2CO3 (139 mg, 1.01 mmol). This mixture was stirred for 48 h. at R.T. All solvent was then removed under reduced pressure, the residue taken up into EtOAc containing 10% MeOH (100 mL), and this solution washed with water (2×100 mL) and brine (100 mL). The combined aqueous fractions were back-extracted with EtOAc (2×100 mL). All EtOAc fractions were combined and dried with Na2SO4, the solvent removed under reduced pressure and the residue purified by column chromatography on silica gel (5% MeOH/CH2Cl2 as eluant). This gave 4-(4-ethynyl-2-fluoroanilino)-N-(2-hydroxyethyl)-6-oxo-1,6-dihydro-3-pyridinecarboxamide as a white solid (152 mg, 96%), m.p. (acetone/MeOH) 265-273° C. 1H NMR [(CD3)2SO, 400 MHz] δ 11.44 (br s, 1H), 10.41 (s, 1H), 8.49 (br t, J=5.1 Hz, 1H), 7.97 (s, 1H), 7.50 (t, J=8.5 Hz, 1H), 7.45 (dd, J=11.5, 1.8 Hz, 1H), 7.33 (dd, J=8.3, 1.4 Hz, 1H), 5.62 (s, 1H), 4.72 (t, J=5.7 Hz, 1H), 4.24 (s, 1H), 3.50 (q, J=5.8 Hz, 2H), 3.31-3.23 (m, 2H). Anal. Calcd for C16H14FN3O3: C, 61.0; H, 4.5; N, 13.3. Found: C, 61.1; H, 4.3; N, 13.3.

Workup

  1. customAll solvent was then removed under reduced pressure
  2. washthis solution washed with water (2×100 mL) and brine (100 mL)
  3. extractionThe combined aqueous fractions were back-extracted with EtOAc (2×100 mL)
  4. dry with materialdried with Na2SO4
  5. customthe solvent removed under reduced pressure
  6. customthe residue purified by column chromatography on silica gel (5% MeOH/CH2Cl2 as eluant)
  7. customThis gave 4-(4-ethynyl-2-fluoroanilino)-N-(2-hydroxyethyl)-6-oxo-1,6-dihydro-3-pyridinecarboxamide as a white solid (152 mg, 96%), m.p. (acetone/MeOH) 265-273° C

Sources & evidence

ORD record
ord-81837b5c87af4cbbbe5971f504055487
Source dataset
uspto-grants-2007_09
Patent number
US07273877B2

Reaction notes

Loading…