Acetic Acid → 5-{4-[5-(4-Fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]butoxy}nicotinic acid

HRID 2102373Notes

Reaction equation

HRID 2102373 reaction equation
C[O:2][C:3](=[O:31])[C:4]1[CH:9]=[C:8]([O:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]2[C:16]3[C:23]([C:24]4[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=4)=[CH:22][S:21][C:17]=3[N:18]=[CH:19][N:20]=2)[CH:7]=[N:6][CH:5]=1.[OH-].[K+].C(O)(=O)C>CO>[F:30][C:27]1[CH:26]=[CH:25][C:24]([C:23]2[C:16]3[C:15]([CH2:14][CH2:13][CH2:12][CH2:11][O:10][C:8]4[CH:7]=[N:6][CH:5]=[C:4]([CH:9]=4)[C:3]([OH:31])=[O:2])=[N:20][CH:19]=[N:18][C:17]=3[S:21][CH:22]=2)=[CH:29][CH:28]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 14797Potassium HydroxideHCID 11647803Methyl 5-4-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]butoxynicotinate

Product 1

HCID 116557445-{4-[5-(4-Fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]butoxy}nicotinic acidYield 82,139.102%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of methyl-5-{4-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]butoxy}nicotinate (0.010 g, 0.023 mmol) and potassium hydroxide (0.0112 g, 0.200 mmol) in methanol (0.5 mL) was stirred at room temperature for 12 h. Acetic acid (200 mg, 3.33 mmol) was then added, and the reaction solvent was removed by evaporation. The product was purified by column chromatography over silica gel using 5% methanol in dichloromethane as eluant to afford 8 g (83%) 5-{4-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]butoxy}nicotinic acid hydroformate as white solid. MS [M+H]=424.1, LC/MS (EI) tR 3.89 min (Method D), 1H NMR (10% MeOD/CDCl3) δ (ppm) 8.94 (s, 1H), 8.73 (s, 1H), 8.28 (s, 1H), 7.68 (s, 1H), 7.40-7.30 (m, 3H), 7.10 (t, J=8.4 Hz, 2H), 3.84 (t, J=6.3 Hz, 2H), 2.68 (t, J=7.2 Hz, 2H), 1.75-1.59 (m, 2H), 1.59-1.45 (m, 2H)

Workup

  1. customthe reaction solvent was removed by evaporation
  2. customThe product was purified by column chromatography over silica gel using 5% methanol in dichloromethane as eluant

Sources & evidence

ORD record
ord-f689128c9b134d8eb33e3ea3cbf8a08c
Source dataset
uspto-grants-2009_08
Patent number
US07576080B2

Reaction notes

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