Toluene → HCID 86614073, compound

HRID 506865Notes

Reaction equation

HRID 506865 reaction equation
[N:1]1([C:7]2[CH:30]=[CH:29][C:10]([CH:11]=[CH:12][C:13]3[C:14](F)=[N:15][CH:16]=[C:17](B4OC(C)(C)C(C)(C)O4)[CH:18]=3)=[CH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl[C:32]1[CH:37]=[CH:36][N:35]=[C:34]([NH:38][CH3:39])[N:33]=1.C1(C)C=CC=CC=1.C([O-])([O-])=[O:48].[K+].[K+]>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.CCO>[N:1]1([C:7]2[CH:8]=[CH:9][C:10]([CH:11]=[CH:12][C:13]3[C:14](=[O:48])[NH:15][CH:16]=[C:17]([C:32]4[CH:37]=[CH:36][N:35]=[C:34]([NH:38][CH3:39])[N:33]=4)[CH:18]=3)=[CH:29][CH:30]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

7

Reactant 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 123976804-Chloro-N-methylpyrimidin-2-amineHCID 66917473HCID 66917473, compound

Product 1

HCID 86614073HCID 86614073, compoundYield 21.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
110 °C

Procedure

A 100 mL round-bottomed flask was charged with 3-(4-(piperidin-1-yl)styryl)-2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (199 mg, 0.49 mmol), 4-chloro-N-methylpyrimidin-2-amine (146 mg, 1.016 mmol) and Pd(PPh3)4 (59 mg, 50.9 μmol). Then toluene (20 mL), EtOH (10 mL) and 2M aq. K2CO3 (1.53 mL, 3.05 mmol) were added and the reaction mixture was immersed in an oil bath at 120° C. for 1 h. The reaction mixture was partitioned between EtOAc (30 mL) and water (50 mL) and the organic layer was dried (MgSO4), filtered and concentrated and then quickly filtered through silica (MeOH/CH2Cl2 gradient). After evaporation of volatiles the residue was dissolved in dioxane (8 mL) and water (3 mL) and concentrated HCl (0.66 mL) was added. The reaction mixture was heated to 110° C. for 70 min and then evaporated. Purification by reverse phase preparative HPLC (eluting with aq. TFA/MeCN) gave the title compound (40 mg, 21%) as a yellow solid.

Workup

  1. customThe reaction mixture was partitioned between EtOAc (30 mL) and water (50 mL)
  2. dry with materialthe organic layer was dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. filtrationquickly filtered through silica (MeOH/CH2Cl2 gradient)
  6. customAfter evaporation of volatiles the residue
  7. dissolutionwas dissolved in dioxane (8 mL)
  8. additionwater (3 mL) and concentrated HCl (0.66 mL) was added
  9. customevaporated
  10. customPurification
  11. washby reverse phase preparative HPLC (eluting with aq. TFA/MeCN)

Sources & evidence

ORD record
ord-f8c67af390ce4951819ab1759d37ace2
Source dataset
uspto-grants-2010_08
Patent number
US07786120B2

Reaction notes

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