Potassium Carbonate → HCID 58102805, compound

HRID 450190Notes

Reaction equation

HRID 450190 reaction equation
Cl[C:2]1[CH:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[N:5]=[C:4]([N:14]2[C:18]3[CH:19]=[CH:20][CH:21]=[C:22]([O:23][CH3:24])[C:17]=3[N:16]=[C:15]2[CH:25]([F:27])[F:26])[N:3]=1.[N:28]1[CH:33]=[C:32](B(O)O)[CH:31]=[N:30][CH:29]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:26][CH:25]([F:27])[C:15]1[N:14]([C:4]2[N:3]=[C:2]([C:32]3[CH:33]=[N:28][CH:29]=[N:30][CH:31]=3)[CH:7]=[C:6]([N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)[N:5]=2)[C:18]2[CH:19]=[CH:20][CH:21]=[C:22]([O:23][CH3:24])[C:17]=2[N:16]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 86649779HCID 86649779, compound

Product 1

HCID 58102805HCID 58102805, compoundYield 75.6%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

Similarly to Example 55, a mixture of 1-[4-chloro-6-(4-morpholinyl)-2-pyrimidinyl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazole (106 mg, 0.268 mmol), pyrimidine-5-boronic acid (188 mg, 1.52 mmol), PdCl2(dppf) (40 mg, 0.05 mmol) and aq. K2CO3 (2M, 4 mL) in 1,4-dioxane (20 mL) was refluxed under nitrogen for 24 hrs. After cooling to room temperature, the mixture was diluted with H2O, and extracted with CH2Cl2 (4×). The combined organic extracts were dried (Na2SO4), and the solvents removed under vacuum. Chromatography on silica, eluting with CH2Cl2/MeOH (100:0 to 97:3), followed by recrystallization from CH2Cl2/MeOH/hexanes gave 2-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-4,5′-bipyrimidine (89 mg, 75%): mp 222-224° C.; 1H NMR (CDCl3) δ 9.38 (s, 2H), 9.36 (s, 1H), 7.92 (dd, J=8.4, 0.6 Hz, 1H), 7.49 (t, J=53.6 Hz, 1H), 7.38 (t, J=8.2 Hz, 1H), 6.86 (s, 1H), 6.84 (d, J=7.7 Hz, 1H), 4.07 (s, 3H), 3.89 (m, 4H), 3.85 (m, 4H); Anal. Calcd. for C21H19F2N7O20.25 MeOH: C, 57.0; H, 4.5; N, 21.9. Found: C, 56.95; H, 4.45; N, 22.0%.

Workup

  1. temperaturewas refluxed under nitrogen for 24 hrs
  2. extractionextracted with CH2Cl2 (4×)
  3. dry with materialThe combined organic extracts were dried (Na2SO4)
  4. customthe solvents removed under vacuum
  5. washChromatography on silica, eluting with CH2Cl2/MeOH (100:0 to 97:3)
  6. customfollowed by recrystallization from CH2Cl2/MeOH/hexanes

Sources & evidence

ORD record
ord-ce6f821bb17e4c0c9098faeaa6f3b416
Source dataset
uspto-grants-2013_07
Patent number
US08486939B2

Reaction notes

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