Hydrochloric Acid → HCID 57636130, compound

HRID 216235Notes

Reaction equation

HRID 216235 reaction equation
Cl.[CH3:2][O:3][C:4]1[N:9]=[C:8]([C:10]2[CH:11]=[C:12]([C:16]3([C:22]([OH:24])=[O:23])[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)[CH:13]=[CH:14][CH:15]=2)[CH:7]=[C:6]([NH:25][CH2:26][CH2:27][C:28]2[CH:33]=[CH:32][C:31]([O:34][C:35]([F:38])([F:37])[F:36])=[CH:30][CH:29]=2)[N:5]=1.[CH3:39]O>>[CH3:39][O:23][C:22]([C:16]1([C:12]2[CH:13]=[CH:14][CH:15]=[C:10]([C:8]3[CH:7]=[C:6]([NH:25][CH2:26][CH2:27][C:28]4[CH:29]=[CH:30][C:31]([O:34][C:35]([F:37])([F:38])[F:36])=[CH:32][CH:33]=4)[N:5]=[C:4]([O:3][CH3:2])[N:9]=3)[CH:11]=2)[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1)=[O:24]

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 887MethanolHCID 86615706HCID 86615706, compound

Product 1

HCID 57636130HCID 57636130, compound

Conditions

Temperature
70 °C

Procedure

Hydrogen chloride (4 M in 1,4-dioxane, 43.5 μL, 0.17 mmol) is added to a solution of N-[4-(3-{2-methoxy-6-[2-(4-trifluoromethoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-phenyl)-tetrahydro-pyran-4-carboxylic acid (45 mg, 0.09 mmol) in methyl alcohol (4 mL) and the reaction mixture is stirred overnight at 70° C. The reaction is cooled to room temperature, quenched with water. The volatiles are removed in vacuo. The aqueous is extracted twice with ethyl acetate. The combined extracts are dried over sodium sulfate, filtered and concentrated in vacuo. The residue is purified by chromatography (SiO2 packed column), eluted with ethyl acetate/heptane to afford 4-(3-{2-methoxy-6-[2-(4-trifluoromethoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-phenyl)-tetrahydro-pyran-4-carboxylic acid methyl ester [86 mg, Example 84(b)]. LCMS: RT=2.48 minutes, MS: 532 (M+H). IC50=70 nM

Workup

  1. temperatureThe reaction is cooled to room temperature
  2. customquenched with water
  3. customThe volatiles are removed in vacuo
  4. extractionThe aqueous is extracted twice with ethyl acetate
  5. dry with materialThe combined extracts are dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue is purified by chromatography (SiO2 packed column)
  9. washeluted with ethyl acetate/heptane

Sources & evidence

ORD record
ord-14679eedda4c4b61a97d0cccec46a2fa
Source dataset
uspto-grants-2012_06
Patent number
US08193183B2

Reaction notes

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