Methanol → 3-(2-Chloro-phenyl)-6-fluoro-2-(pyrimidin-2-ylaminomethyl)-3h-quinazolin-4-one

HRID 897026Notes

Reaction equation

HRID 897026 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:17](=[O:18])[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([F:19])[CH:15]=2)[N:10]=[C:9]1[CH:20]=O.CO.[NH2:24][C:25]1[N:30]=[CH:29][CH:28]=[CH:27][N:26]=1.[OH-].[Na+]>[Pd].C(O)=O>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:17](=[O:18])[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([F:19])[CH:15]=2)[N:10]=[C:9]1[CH2:20][NH:24][C:25]1[N:30]=[CH:29][CH:28]=[CH:27][N:26]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 79782-AminopyrimidineHCID 14798Sodium HydroxideHCID 106858093-(2-Chlorophenyl)-6-fluoro-3,4-dihydroquinazolin-4-one-2-carboxaldehyde

Product 1

HCID 102373773-(2-Chloro-phenyl)-6-fluoro-2-(pyrimidin-2-ylaminomethyl)-3h-quinazolin-4-one

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 284Formic AcidSolvent

Procedure

A mixture of 3-(2-chloro-phenyl)-6-fluoro-3,4-dihydro-quinazolin-4-one-2-carboxaldehyde (0.200 g, 0.66 mmol), methanol (20 mL), and 2-aminopyrimidine (0.059 g, 0.62 mmol) was refluxed 29 hours. The mixture was cooled to room temperature and 10% palladium on carbon (0.236 g) and formic acid (1.1 mL) were added. The mixture was allowed to stir at ambient temperature overnight. The reaction was treated with 6 N sodium hydroxide to adjust the pH to 10. The mixture was filtered through celite and the pad was washed with ethyl acetate. The filtrate was dried over magnesium sulfate and concentrated. The residue was flash chromatographed on silica gel (20 g) with elution proceeding as follows: 10% ethyl acetate/hexane (500 mL), nil; 20% ethyl acetate/hexane (250 mL), unweighed impurity, 20% ethyl acetate/hexane (100 mL), mixed fraction, unweighed; 20% ethyl acetate/hexane (150 mL) and 30% ethyl acetate/hexane (150 mL), unweighed 3-(2-chloro-phenyl)-6-fluoro-3,4-dihydro-quinazolin-4-one-2-methanol (a side product). Elution was continued: 30% ethyl acetate/hexane 410 mL), nil; 40% ethyl acetate/hexane (450 mL), nil; 40% ethyl acetate/hexane (50 mL) and 50% ethyl acetate/hexane (450 mL), 0.028 g (8%) of 3-(2-Chloro-phenyl)-6-fluoro-2-(pyrimidin-2-ylaminomethyl)-3H-quinazolin-4-one as a white solid which had: mp 182-185° C.; 1H NMR δ 8.29 (d, J=5 Hz, 2 H), 7.92 (dd, J=3, 8 Hz, 1 H), 7.82 (dd, J=5, 9 Hz, 1 H), 7.66-7.64 (m, 1 H), 7.55-7.49 (m, 3 H), 7.40-7.38 (m, 1 H), 6.63 (t, J=5 Hz, 1 H), 4.28 (dd, J=4.5, 18 Hz, 1 H), 4.11 (dd, J=4, 18 Hz, 1 H). Analysis calculated for C19H11ClFN5O.0.75 H2O: C, 58.05; H, 3.20; N, 17.81. Found: C, 58.06; H, 3.25; N, 17.33. APCI MS m/z=382 (P+1).

Workup

  1. temperaturewas refluxed 29 hours
  2. filtrationThe mixture was filtered through celite
  3. washthe pad was washed with ethyl acetate
  4. dry with materialThe filtrate was dried over magnesium sulfate
  5. concentrationconcentrated
  6. customchromatographed on silica gel (20 g) with elution proceeding
  7. addition20% ethyl acetate/hexane (250 mL), unweighed impurity, 20% ethyl acetate/hexane (100 mL), mixed fraction
  8. washElution

Sources & evidence

ORD record
ord-cee05436cb8f47f69fa4ed6a5bb2cd3c
Source dataset
uspto-grants-2005_07
Patent number
US06921764B2

Reaction notes

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