Sodium Carbonate → HCID 178488058, compound

HRID 2367392Notes

Reaction equation

HRID 2367392 reaction equation
Cl[C:2]1[CH:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH:10]([C:14]3[NH:18][C:17]4[CH:19]=[CH:20][C:21]([O:23][CH3:24])=[CH:22][C:16]=4[N:15]=3)[CH2:9]2)[N:5]=[C:4]([NH2:25])[N:3]=1.[F:26][C:27]1[CH:34]=[C:33](B2OC(C)(C)C(C)(C)O2)[CH:32]=[CH:31][C:28]=1[C:29]#[N:30].C([O-])([O-])=O.[Na+].[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:4]1[N:3]=[C:2]([C:33]2[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[C:27]([F:26])[CH:34]=2)[CH:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH:10]([C:14]3[NH:18][C:17]4[CH:19]=[CH:20][C:21]([O:23][CH3:24])=[CH:22][C:16]=4[N:15]=3)[CH2:9]2)[N:5]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 513509512-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrileHCID 178488059HCID 178488059, compound

Product 1

HCID 178488058HCID 178488058, compoundYield 97.1%

Reagents, catalysts & solvents 3

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

Procedure

To a solution of 4-chloro-6-{2-[5-(methyloxy)-1H-benzimidazol-2-yl]-4-morpholinyl}-2-pyrimidinamine (150 mg, 0.416 mmol), 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (134 mg, 0.540 mmol) and Na2CO3 (110 mg, 1.039 mmol) in 1,4-dioxane (1.8 mL) and water (0.6 mL) stirred under nitrogen at room temperature was added solid Pd(PPh3)4 (48.0 mg, 0.042 mmol) in one charge. The reaction vessel was sealed and heated in Biotage Initiator using initial high to 140° C. for 1 hour. The reaction mixture was partitioned between EtOAc/THF 25/25 mL and water 50 mL. The organic phase was washed with water (50 mL), dried (Na2SO4) and concentrated in vacuo. The crude product was added to a silica gel column and was eluted with Hexanes/EtOAc to afford the title compound (180 mg). LC-MS (ES) m/z=446 [M+H]+.

Workup

  1. additioncharge
  2. customThe reaction vessel was sealed
  3. temperatureheated in Biotage Initiator
  4. customhigh to 140° C.
  5. customfor 1 hour
  6. customThe reaction mixture was partitioned between EtOAc/THF 25/25 mL and water 50 mL
  7. washThe organic phase was washed with water (50 mL)
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated in vacuo
  10. additionThe crude product was added to a silica gel column
  11. washwas eluted with Hexanes/EtOAc

Sources & evidence

ORD record
ord-c9fe7981254847699881f5ac96aaef86
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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