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

HRID 522727Notes

Reaction equation

HRID 522727 reaction equation
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

Participants

7

Reactant 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×

Product 1

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

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-1d421c0c404a4df1ae8a4dbe2d4c567e
Source dataset
uspto-grants-2016_05
Patent number
US09334267B2

Reaction notes

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