Diisopropylethylamine → (2-Cyclopropyl-6-chloro-5-methyl-pyrimidin-4-yl]-[1,8]naphthyridine

HRID 1169809노트

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HRID 1169809 반응식
C(N(C(C)C)CC)(C)C.[CH:10]1([C:13]2[N:18]=[C:17]([Cl:19])[C:16]([CH3:20])=[C:15](Cl)[N:14]=2)[CH2:12][CH2:11]1.N1CCC([C:28]2[CH:37]=[CH:36][C:35]3[C:30](=[N:31][CH:32]=[CH:33][CH:34]=3)[N:29]=2)CC1.N1C2C(=CC=CN=2)C=CC=1.C(=O)(O)[O-].[Na+]>O.C(OCC)(=O)C.CC(N(C)C)=O>[CH:10]1([C:13]2[N:14]=[C:15]([C:28]3[CH:37]=[CH:36][C:35]4[C:30](=[N:31][CH:32]=[CH:33][CH:34]=4)[N:29]=3)[C:16]([CH3:20])=[C:17]([Cl:19])[N:18]=2)[CH2:11][CH2:12]1

참가 물질

9

반응물 5

HCID 81531DiisopropylethylamineHCID 1360691,8-NaphthyridineHCID 516892Sodium BicarbonateHCID 545957314,6-Dichloro-2-cyclopropyl-5-methylpyrimidineHCID 666409192-(Piperidin-4-YL)-1,8-naphthyridine

생성물 1

HCID 86761204(2-Cyclopropyl-6-chloro-5-methyl-pyrimidin-4-yl]-[1,8]naphthyridine수율 66.1%

시약·촉매·용매 3

HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 31374Dimethylacetamide용매

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온도
100 °C

실험 절차

20 ml of dimethylacetamide and 3.36 ml (19.2 mmoles) of diisopropylethylamine are added into a single-necked flask containing 1.5 g (7.39 mmoles) of 2-cyclopropyl-4,6-dichloro-5-methyl-pyrimidine and 1.58 g (7.39 mmoles) of 2-piperidin-4-yl-[1,8]naphthyridine. This mixture is heated at 100° C. overnight. The next day 0.2 equivalent of naphthyridine is added and the reaction mixture is heated for another 6 hours, followed by returning to ambient temperature before concentration to dryness. The residue obtained is taken up in a mixture of water, ethyl acetate and a saturated solution of sodium bicarbonate. The organic phase is separated and the aqueous phase reextracted with ethyl acetate. The collected organic phases are dried over magnesium sulphate then the solvent is evaporated off under reduced pressure (2 kPa). The residue is chromatographed on silica gel eluting with a gradient of heptane-ethyl acetate (50-50) to 100% ethyl acetate, 1.45 g of expected product is obtained.

후처리

  1. temperaturethe reaction mixture is heated for another 6 hours
  2. concentrationby returning to ambient temperature before concentration to dryness
  3. customThe residue obtained
  4. customThe organic phase is separated
  5. dry with materialThe collected organic phases are dried over magnesium sulphate
  6. customthe solvent is evaporated off under reduced pressure (2 kPa)
  7. customThe residue is chromatographed on silica gel eluting with a gradient of heptane-ethyl acetate (50-50) to 100% ethyl acetate

출처 및 근거

ORD 기록
ord-70a61eec63e4482caa4dbe0d8319cd2d
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07825119B2

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