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

HRID 1169267노트

반응식

HRID 1169267 반응식
[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

참가 물질

8

반응물 4

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

생성물 1

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

시약·촉매·용매 3

HCID 23938Palladium촉매HCID 702Ethanol용매HCID 887Methanol용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-547e7eb0df164797953eb7e4581d53f4
출처 데이터셋
uspto-grants-2003_09
특허 번호
US06627755B1

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