Hydrochloric Acid → HCID 11647546, compound

HRID 2102372Notes

Reaction equation

HRID 2102372 reaction equation
C[O:2][C:3](=[O:31])[C:4]1[CH:9]=[C:8]([O:10][CH2:11][CH2:12][CH2:13][O: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-].[Li+].Cl>O1CCOCC1.O>[F:30][C:27]1[CH:28]=[CH:29][C:24]([C:23]2[C:16]3[C:15]([O: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:25][CH:26]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 11503064HCID 11503064, compound

Product 1

HCID 11647546HCID 11647546, compoundYield 93%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 5-{3-[5-(4-fluorophenyl)-thieno[2,3-d]pyrimidin-4-yloxy]-propoxy}-nicotinic acid methyl ester (100 mg) in dioxane (10 mL) was added 0.80 M lithium hydroxide in water (2.0 mL). The reaction was stirred at ambient temperature for 16 hours, then acidified with 1M hydrochloric acid to pH 3, and the solvent removed under reduced pressure. The residue was dissolved in 20% methanol/dichloromethane (40 mL), filtered, and the filtrate was concentrated. The product was purified by column chromatography over silica gel using 10% methanol in dichloromethane as eluant to give 90 mg (93%) of 5-{3-[5-(4-fluorophenyl)-thieno[2,3-d]pyrimidin-4-yloxy]-propoxy}-nicotinic acid as a white solid. MS [M+H] 425.9, 1H NMR (CD3OD) δ (ppm) 8.91 (s, 1H), 8.63 (s, 1H), 8.62 (s, 1H), 8.27 (s, 1H), 7.60-7.45 (m, 3H), 7.10 (t, J=8.7 Hz, 2H), 4.67 (t, J=9.0 Hz, 2H), 3.94 (t, J=9.3 Hz, 2H), 2.22 (t, J=9.0 Hz, 2H).

Workup

  1. customthe solvent removed under reduced pressure
  2. dissolutionThe residue was dissolved in 20% methanol/dichloromethane (40 mL)
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated
  5. customThe product was purified by column chromatography over silica gel using 10% methanol in dichloromethane as eluant

Sources & evidence

ORD record
ord-a3bd729efa68482b9702eab43c444de2
Source dataset
uspto-grants-2009_08
Patent number
US07576080B2

Reaction notes

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