Potassium Carbonate → 1-(3,3-Dimethylbutyl)-3-(2-fluoro-4-methyl-5-(7-methyl-2-(methylthio)pyrido[2,3-d]pyrimidin-6-yl)phenyl)urea

HRID 522717Notes

Reaction equation

HRID 522717 reaction equation
[CH3:1][C:2]([CH3:27])([CH3:26])[CH2:3][CH2:4][NH:5][C:6]([NH:8][C:9]1[CH:14]=[C:13](B2OC(C)(C)C(C)(C)O2)[C:12]([CH3:24])=[CH:11][C:10]=1[F:25])=[O:7].FC(F)(F)S(O[C:34]1[C:45]([CH3:46])=[N:44][C:37]2[N:38]=[C:39]([S:42][CH3:43])[N:40]=[CH:41][C:36]=2[CH:35]=1)(=O)=O.C([O-])([O-])=O.[K+].[K+]>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>[CH3:27][C:2]([CH3:1])([CH3:26])[CH2:3][CH2:4][NH:5][C:6]([NH:8][C:9]1[CH:14]=[C:13]([C:34]2[C:45]([CH3:46])=[N:44][C:37]3[N:38]=[C:39]([S:42][CH3:43])[N:40]=[CH:41][C:36]=3[CH:35]=2)[C:12]([CH3:24])=[CH:11][C:10]=1[F:25])=[O:7]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 898092287-Methyl-2-(methylthio)pyrido[2,3-d]pyrimidin-6-yl trifluoromethanesulfonateHCID 898095371-(3,3-Dimethylbutyl)-3-(2-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea

Product 1

HCID 898134311-(3,3-Dimethylbutyl)-3-(2-fluoro-4-methyl-5-(7-methyl-2-(methylthio)pyrido[2,3-d]pyrimidin-6-yl)phenyl)ureaYield 56.4%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Combine 1-(3,3-dimethylbutyl)-3-(2-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (0.669 g, 1.768 mmol), 7-methyl-2-(methylthio)pyrido[2,3-d]pyrimidin-6-yl trifluoromethanesulfonate (0.6 g, 1.768 mmol), K2CO3 (0.733 g, 5.30 mmol) and Pd(PPh3)4 (0.102 g, 0.088 mmol) in dioxane (8 mL) and water (2 mL) in a pressure tube, sparge with argon, seal and heat at 100° C. overnight. Cool the mixture to RT, treat with saturated aqueous. NaHCO3 and extract with EtOAc (3×). Dry the combined organics over MgSO4, concentrate to dryness and purify via silica gel chromatography (5-100% EtOAc/Hexanes) to afford the title compound (440 mg, 56%). MS (m/z): 442.2 (M+1).

Workup

  1. customseal
  2. temperatureCool the mixture to RT
  3. additiontreat with saturated aqueous
  4. extractionNaHCO3 and extract with EtOAc (3×)
  5. dry with materialDry the combined organics over MgSO4
  6. concentrationconcentrate to dryness
  7. custompurify via silica gel chromatography (5-100% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-10a50f28f42f456daa016bffb883e06d
Source dataset
uspto-grants-2016_05
Patent number
US09334267B2

Reaction notes

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