Sodium Bicarbonate → 6-(5-Amino-4-fluoro-2-methylphenyl)-N,7-dimethylpyrido[2,3-d]pyrimidin-2-amine

HRID 522727ノート

反応式

HRID 522727 の反応式
FC(F)(F)S(O[C:7]1[C:18]([CH3:19])=[N:17][C:10]2[N:11]=[C:12]([NH:15][CH3:16])[N:13]=[CH:14][C:9]=2[CH:8]=1)(=O)=O.[F:22][C:23]1[CH:29]=[C:28]([CH3:30])[C:27](B2OC(C)(C)C(C)(C)O2)=[CH:26][C:24]=1[NH2:25].C([O-])(O)=O.[Na+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:25][C:24]1[C:23]([F:22])=[CH:29][C:28]([CH3:30])=[C:27]([C:7]2[C:18]([CH3:19])=[N:17][C:10]3[N:11]=[C:12]([NH:15][CH3:16])[N:13]=[CH:14][C:9]=3[CH:8]=2)[CH:26]=1

参加物

7

反応物 3

HCID 516892Sodium BicarbonateHCID 690365482-Fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 898095047-Methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl trifluoromethanesulfonate2 回

生成物 1

HCID 898135606-(5-Amino-4-fluoro-2-methylphenyl)-N,7-dimethylpyrido[2,3-d]pyrimidin-2-amine収率 89%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒2 回HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
60 °C

実験手順

Combine 7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl trifluoromethanesulfonate (1.15 g, 3.57 mmol), 2-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (0.896 g, 3.57 mmol), and NaHCO3 (0.899 g, 10.71 mmol) in dioxane (24 mL) and H2O (6 mL), sparge with argon, treat with Pd(PPh3)4 (0.206 g, 0.178 mmol) and heat to 60° C. overnight. Add additional 7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl trifluoromethanesulfonate (120 mg, 0.37 mmol) and Pd(PPh3)4 (80 mg, 0.07 mmol), sparge the mixture with argon, and heat at 60° C. overnight. Cool the mixture to RT, treat with brine and extract with EtOAc (3×). Wash the combined organics with brine, dry over Na2SO4, concentrate to dryness and purify via silica gel chromatography (50-100% EtOAc/Hexanes) to afford the title compound (940 mg, 89% yield). MS (m/z): 298.1 (M+1).

後処理

  1. customsparge the mixture with argon
  2. temperatureheat at 60° C. overnight
  3. temperatureCool the mixture to RT
  4. additiontreat with brine
  5. extractionextract with EtOAc (3×)
  6. washWash the combined organics with brine
  7. dry with materialdry over Na2SO4
  8. concentrationconcentrate to dryness
  9. custompurify via silica gel chromatography (50-100% EtOAc/Hexanes)

出典と根拠

ORDレコード
ord-1d421c0c404a4df1ae8a4dbe2d4c567e
出典データセット
uspto-grants-2016_05
特許番号
US09334267B2

反応ノート

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