Potassium Carbonate → HCID 49869215, compound

HRID 450191Notes

Reaction equation

HRID 450191 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.[CH3:28][O:29][C:30]1[N:35]=[CH:34][C:33](B(O)O)=[CH:32][N:31]=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:33]3[CH:32]=[N:31][C:30]([O:29][CH3:28])=[N:35][CH:34]=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 27367782-Methoxypyrimidine-5-boronic acidHCID 86649779HCID 86649779, compound

Product 1

HCID 49869215HCID 49869215, compoundYield 35%

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 56, a mixture of 1-[4-chloro-6-(4-morpholinyl)-2-pyrimidinyl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazole (148 mg, 0.374 mmol), 2-methoxy-5-pyrimidinylboronic acid (211 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 were removed under vacuum. Chromatography on silica, eluting with CH2Cl2/MeOH (100:0 to 98:2), followed by recrystallization from CH2Cl2/MeOH/i-Pr2O gave 2-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-2′-methoxy-4,5′-bipyrimidine (61 mg, 35%): mp 238-241° C.; 1H NMR (CDCl3) δ 9.18 (s, 2H), 7.91 (d, J=8.1 Hz, 1H), 7.49 (t, JHF=53.6 Hz, 1H), 7.37 (t, J=8.2 Hz, 1H), 6.83 (d, J=7.9 Hz, 1H), 6.77 (s, 1H), 4.13 (s, 3H), 4.07 (s, 3H), 3.88 (dd, J=5.6, 3.7 Hz, 4H), 3.82 (m, 4H); Anal. Calcd. for C22H21F2N7O3: C, 56.3; H, 4.5; N, 20.9. Found: C, 56.1; H, 4.3; N, 20.6%.

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 were removed under vacuum
  5. washChromatography on silica, eluting with CH2Cl2/MeOH (100:0 to 98:2)
  6. customfollowed by recrystallization from CH2Cl2/MeOH/i-Pr2O

Sources & evidence

ORD record
ord-597ea97ecbe24afc890971e539f01f55
Source dataset
uspto-grants-2013_07
Patent number
US08486939B2

Reaction notes

Loading…