Morpholine → 2-(4-Methoxyphenyl)-5-morpholinopyridin-3-amine

HRID 1431557노트

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HRID 1431557 반응식
Br[C:2]1[CH:3]=[C:4]([NH2:16])[C:5]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=2)=[N:6][CH:7]=1.C1(P(C2CCCCC2)C2(C(C)C)CC(C(C)C)=CC(C(C)C)=C2C2C=CC=CC=2)CCCCC1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[NH:85]1[CH2:90][CH2:89][O:88][CH2:87][CH2:86]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[CH3:15][O:14][C:11]1[CH:12]=[CH:13][C:8]([C:5]2[C:4]([NH2:16])=[CH:3][C:2]([N:85]3[CH2:90][CH2:89][O:88][CH2:87][CH2:86]3)=[CH:7][N:6]=2)=[CH:9][CH:10]=1

참가 물질

9

반응물 5

HCID 8083MorpholineHCID 2733832Lithium HexamethyldisilazideHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 596313025-Bromo-2-(4-methoxyphenyl)pyridin-3-amineHCID 672859322-Dicyclohexylphosphino-2,4,6-triisopropylbiphenyl

생성물 1

HCID 596312932-(4-Methoxyphenyl)-5-morpholinopyridin-3-amine

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 8028Tetrahydrofuran용매2회

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온도
60 °C

실험 절차

A mixture of 5-bromo-2-(4-methoxyphenyl)pyridin-3-amine (424.5 mg, 1.52 mmol), 2-dicyclohexylphosphino-2,4,6,-triisopropylbiphenyl, (X-Phos) (58.8 mg, 0.12 mmol), tris(dibenzylideneacetone)dipalladium (0) (56.1 mg, 0.061 mmol), and morpholine (0.66 mL, 7.58 mmol) in dry THF (3.2 mL) was degassed by nitrogen. To this mixture was added lithium bis(trimethylsilyl)amide, 1.0M in THF (8.4 mL, 8.40 mmol) dropwise, and the resulting reaction was heated to 60° C. After 2.5 h, the reaction was cooled to rt then poured into water. After extracting twice with EtOAc and twice with DCM, the combined organic layers were dried over anhydrous magnesium sulfate. After filtration and concentration, the residue was purified on silica gel (0-100% DCM in EtOAc) to yield 2-(4-methoxyphenyl)-5-morpholinopyridin-3-amine. 1H NMR (400 MHz, CDCl3) δ ppm 7.84 (1H, d, J=2.5 Hz), 7.57 (2H, m), 6.98 (2H, m), 6.53 (1H, d, J=2.5 Hz), 3.92 (9H, m), 3.22 (4H, m). Mass Spectrum (pos.) m/e: 286.1 (M+1).

후처리

  1. customwas degassed by nitrogen
  2. customthe resulting reaction
  3. temperaturethe reaction was cooled to rt
  4. extractionAfter extracting twice with EtOAc and twice with DCM
  5. dry with materialthe combined organic layers were dried over anhydrous magnesium sulfate
  6. filtrationAfter filtration and concentration
  7. customthe residue was purified on silica gel (0-100% DCM in EtOAc)

출처 및 근거

ORD 기록
ord-bc39388298bb46919c16908e804fcd0f
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08940724B2

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