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

HRID 897026ノート

反応式

HRID 897026 の反応式
[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

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 23938Palladium触媒HCID 284Formic Acid溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-cee05436cb8f47f69fa4ed6a5bb2cd3c
出典データセット
uspto-grants-2005_07
特許番号
US06921764B2

反応ノート

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