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

HRID 522727노트

반응식

HRID 522727 반응식
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

참가 물질

7

반응물 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 trifluoromethanesulfonate2회

생성물 1

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

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매2회HCID 962Water용매HCID 312751,4-Dioxane용매

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온도
60 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-1d421c0c404a4df1ae8a4dbe2d4c567e
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09334267B2

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