Hydrochloric Acid → HCID 57636077, compound

HRID 216229Notes

Reaction equation

HRID 216229 reaction equation
Cl.[Cl:2][C:3]1[CH:8]=[C:7]([Cl:9])[CH:6]=[CH:5][C:4]=1[CH2:10][CH2:11][NH:12][C:13]1[N:18]=[C:17]([O:19][CH3:20])[N:16]=[C:15]([C:21]2[CH:22]=[C:23]([C:27]3([C:33]([OH:35])=[O:34])[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)[CH:24]=[CH:25][CH:26]=2)[CH:14]=1.[CH2:36](O)[CH3:37]>>[CH2:36]([O:34][C:33]([C:27]1([C:23]2[CH:24]=[CH:25][CH:26]=[C:21]([C:15]3[CH:14]=[C:13]([NH:12][CH2:11][CH2:10][C:4]4[CH:5]=[CH:6][C:7]([Cl:9])=[CH:8][C:3]=4[Cl:2])[N:18]=[C:17]([O:19][CH3:20])[N:16]=3)[CH:22]=2)[CH2:28][CH2:29][O:30][CH2:31][CH2:32]1)=[O:35])[CH3:37]

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 702EthanolHCID 11584210HCID 11584210, compound

Product 1

HCID 57636077HCID 57636077, compound

Conditions

Temperature
75 °C

Procedure

Hydrogen chloride (4 M in 1,4-dioxane, 20 μL, 0.08 mmol) is added to a solution of 4-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-tetrahydro-pyran-4-carboxylic acid [20 mg, 0.04 mmol, Example 80(a)] in ethyl alcohol (4 mL) and the reaction mixture is stirred overnight at 75° C. The reaction is cooled to room temperature, quenched with water, 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), eluting with ethyl acetate/heptane to afford 4-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-tetrahydro-pyran-4-carboxylic acid ethyl ester [16 mg, Example 80(c)]. LCMS: RT=2.74 minutes; MS: 530, 532 (M+H); 1H NMR (300 MHz, CDCl3): □8.05 (1H, s), 7.9 (1H, d, J=3.5 Hz), 7.4-7.55 (3H, m), 7.2 (2H, s), 6.4 (1H, s), 5 (1H, b), 4.18 (2H, q, J=2 Hz), 4.05 (3H, s), 3.98 (2H, m), 3.75 (2H, b), 3.65 (2H, t, J=3.5 Hz), 3.1 (2H, t, J=2 Hz), 2.6 (2H, d, J=4 Hz), 2.1 (2H, m), 1.2 (3H, t, J=2 Hz). IC50=223 nM

Workup

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

Sources & evidence

ORD record
ord-578eed5caec44d8f842b904e08b29e95
Source dataset
uspto-grants-2012_06
Patent number
US08193183B2

Reaction notes

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