Formic Acid → 3-(2-Chloro-phenyl)-6-fluoro-2-[(6-methyl-pyridin-2-ylamino)-methyl]-3h-quinazolin-4-one

HRID 1169267ノート

反応式

HRID 1169267 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.[NH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([CH3:29])[N:24]=1.C(O)=O.C(=O)(O)[O-].[Na+]>CO.C(O)C.[Pd]>[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:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([CH3:29])[N:24]=1

参加物

8

反応物 4

HCID 284Formic AcidHCID 157652-Amino-6-methylpyridineHCID 516892Sodium BicarbonateHCID 106858093-(2-Chlorophenyl)-6-fluoro-3,4-dihydroquinazolin-4-one-2-carboxaldehyde

生成物 1

HCID 102375793-(2-Chloro-phenyl)-6-fluoro-2-[(6-methyl-pyridin-2-ylamino)-methyl]-3h-quinazolin-4-one収率 82%

試薬・触媒・溶媒 3

HCID 23938Palladium触媒HCID 702Ethanol溶媒HCID 887Methanol溶媒

実験手順

A mixture of 3-(2-chloro-phenyl)-6-fluoro-3,4-dihydro-quinazolin-4-one-2-carboxaldehyde (0.170 g, 0.56 mmol) and 2-amino-6-picoline (0.050 g, 0.46 mmol), in methanol (10 mL) was refluxed overnight. The reaction was concentrated and the residue was flash chromatographed on silica gel (25 g). Elution proceeded as follows: 10% ethyl acetate/hexane (500 mL), nil; 20% ethyl acetate t hexane (300 mL), nil; (100 mL), 0.082 g of intermediate imine; (300 mL), 0.192 g of a mixture of starting material and imine. The pure imine (0.082 g 0.21 mmol) was dissolved in ethanol (10 mL) and 10% palladium on carbon (0.082 g) and formic acid (0.357 mL, 9.45 mmol) were added. The reaction was stirred at ambient temperature for 24 hours. The reaction was carefully neutralized with sodium bicarbonate and then filtered through celite. The pad was well washed with ethyl acetate. The filtrate was concentrated to afford 0.068 g (82%) of 3-(2-chloro-phenyl)-6-fluoro-2-[(6-methyl-pyridin-2-ylamino)-methyl]-3H-quinazolin-4-one as a colorless oil which had: 1H NMR δ 7.92 (dd, J=3, 8 Hz, 1H), 7.80 (dd, J=5, 9 Hz, 1H), 7.65-7.64 (m, 1H), 7.53-7.48 (m, 4H), 7.43-7.40 (m, 1H), 7.37-7.31 (m, 1H), 6.47 (d, J=7 Hz, 1H), 6.25 (d, J=8 Hz, 1H), 4.18 (dd, J=5, 18 Hz, 1H), 4.00 (dd, J=5, 18 Hz, 1H), 2.37 (s, 3H); APCI MS m/z=395 (P+1).

後処理

  1. concentrationThe reaction was concentrated
  2. customchromatographed on silica gel (25 g)
  3. washElution
  4. filtrationfiltered through celite
  5. washThe pad was well washed with ethyl acetate
  6. concentrationThe filtrate was concentrated

出典と根拠

ORDレコード
ord-547e7eb0df164797953eb7e4581d53f4
出典データセット
uspto-grants-2003_09
特許番号
US06627755B1

反応ノート

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