Sodium Carbonate → HCID 178509574, compound

HRID 2367407Notes

Reaction equation

HRID 2367407 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]([Cl:23])=[CH:22][C:16]=4[N:15]=3)[CH2:9]2)[N:5]=[C:4]([NH2:24])[N:3]=1.[F:25][C:26]1[CH:33]=[C:32](B2OC(C)(C)C(C)(C)O2)[CH:31]=[CH:30][C:27]=1[C:28]#[N:29].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>[NH2:24][C:4]1[N:3]=[C:2]([C:32]2[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[C:26]([F:25])[CH:33]=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]([Cl:23])=[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 178508440HCID 178508440, compound

Product 1

HCID 178509574HCID 178509574, compoundYield 56.8%

Reagents, catalysts & solvents 3

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

Procedure

To a suspension of 4-chloro-6-(2-(5-chloro-1H-benzo[d]imidazol-2-yl)morpholino)pyrimidin-2-amine (200 mg, 0.548 mmol), 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (176 mg, 0.712 mmol) and Na2CO3 (145 mg, 1.369 mmol) in 1,4-dioxane (2.4 mL) and water (0.8 mL) under nitrogen was added Pd(PPh3)4 (63.3 mg, 0.055 mmol). 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 m, dried (Na2SO4) and evaporated in vacuo. The residue was triturated with EtOAc (1×10 mL). The resulting solid was filtered through a coarse fritted glass funnel and collected to afford the title compound (140 mg). LC-MS (ES) m/z=450 [M+H]+.

Workup

  1. customThe reaction vessel was sealed
  2. temperatureheated in Biotage Initiator
  3. customhigh to 140° C.
  4. customfor 1 hour
  5. customThe reaction mixture was partitioned between EtOAc/THF (25/25 mL) and water (50 mL)
  6. washThe organic phase was washed with water (50 m
  7. dry with materialdried (Na2SO4)
  8. customevaporated in vacuo
  9. customThe residue was triturated with EtOAc (1×10 mL)
  10. filtrationThe resulting solid was filtered through a coarse fritted glass funnel
  11. customcollected

Sources & evidence

ORD record
ord-c08b36afe97941d09d6943058861b9f1
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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