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Potassium Phosphate, Tribasic → 5,7-difluoro-3-methyl-N-(2-(4-(methylsulfonyl)phenyl)-5-morpholinopyridin-3-yl)-2-(pyridin-2-yl)quinolin-4-amine

HRID 1431589
ノート
印刷プレビュー

反応式

HRID 1431589 の反応式
Cl[C:2]1[C:7]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([F:20])=[CH:16][C:17]=3[F:19])[N:12]=[C:11]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=3)[C:10]=2[CH3:27])=[CH:6][C:5]([N:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)=[CH:4][N:3]=1.[CH3:34][S:35]([C:38]1[CH:43]=[CH:42][C:41](B(O)O)=[CH:40][CH:39]=1)(=[O:37])=[O:36].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>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.O1CCOCC1>[F:19][C:17]1[CH:16]=[C:15]([F:20])[CH:14]=[C:13]2[C:18]=1[C:9]([NH:8][C:7]1[C:2]([C:41]3[CH:42]=[CH:43][C:38]([S:35]([CH3:34])(=[O:37])=[O:36])=[CH:39][CH:40]=3)=[N:3][CH:4]=[C:5]([N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[CH:6]=1)=[C:10]([CH3:27])[C:11]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=1)=[N:12]2
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 27343644-(Methanesulfonyl)phenylboronic acidHCID 59631201N-(2-Chloro-5-morpholinopyridin-3-yl)-5,7-difluoro-3-methyl-2-(pyridin-2-yl)-quinolin-4-amine

生成物 1

HCID 509073875,7-difluoro-3-methyl-N-(2-(4-(methylsulfonyl)phenyl)-5-morpholinopyridin-3-yl)-2-(pyridin-2-yl)quinolin-4-amine

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
90 °C

実験手順

N-(2-chloro-5-morpholinopyridin-3-yl)-5,7-difluoro-3-methyl-2-(pyridin-2-yl)-quinolin-4-amine (60.7 mg, 0.13 mmol), 4-(methylsulfonyl)phenylboronic acid (40.1 mg, 0.2 mmol), tricyclohexylphosphine (6.2 mg, 0.022 mmol), and tris(dibenzylideneacetone)dipalladium (0) (10.4 mg, 0.011 mmol) were added to a flask then degassed and backfilled with argon. To the flask, 1,4-dioxane (2.0 mL) and aq. 1.3M potassium phosphate tribasic (0.3 mL, 0.39 mmol) were added by syringe. The resulting reaction was heated to 90° C. and monitored with TLC and LC-MS. After 19 h, the reaction was cooled to rt then poured into water. After extracting twice with EtOAc and twice with DCM, the combined organic extractions were dried over anhydrous magnesium sulfate. After filtration and concentration, the residue was purified on silica gel (0-60% of a premixed solution of 89:9:1 DCM:MeOH:ammonium hydroxide in DCM) to afford a film that was triturated with MeOH to afford a light yellow solid as 5,7-difluoro-3-methyl-N-(2-(4-(methylsulfonyl)phenyl)-5-morpholinopyridin-3-yl)-2-(pyridin-2-yl)quinolin-4-amine. 1H NMR (500 MHz, CDCl3) δ ppm 8.69 (1H, dt, J=4.8, 1.2 Hz), 8.12 (5H, m), 7.96 (2H, m), 7.62 (1H, d, J=8.8 Hz), 7.39 (1H, ddd, J=6.8, 4.8, 2.1 Hz), 7.02 (2H, m), 6.55 (1H, d, J=2.4 Hz), 3.91 (4H, m), 3.28 (4H, m), 3.09 (3H, s), 2.25 (3H, s). Mass Spectrum (pos.) m/e: 602.0 (M+1).

後処理

  1. customthen degassed
  2. customThe resulting reaction
  3. temperaturethe reaction was cooled to rt
  4. extractionAfter extracting twice with EtOAc and twice with DCM
  5. extractionthe combined organic extractions
  6. dry with materialwere dried over anhydrous magnesium sulfate
  7. filtrationAfter filtration and concentration
  8. customthe residue was purified on silica gel (0-60% of a premixed solution of 89:9:1 DCM:MeOH:ammonium hydroxide in DCM)
  9. customto afford a film that
  10. customwas triturated with MeOH

出典と根拠

ORDレコード
ord-00da4bef6bec48b5a426be45e48a487b
出典データセット
uspto-grants-2015_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08940724B2

反応ノート

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