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

HRID 1431557ノート

反応式

HRID 1431557 の反応式
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

参加物

9

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
60 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-bc39388298bb46919c16908e804fcd0f
出典データセット
uspto-grants-2015_01
特許番号
US08940724B2

反応ノート

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