Sodium Carbonate → HCID 58504450, compound

HRID 2367599Notes

Reaction equation

HRID 2367599 reaction equation
Cl[C:2]1[CH:7]=[C:6]([N:8]2[C@H:13]([CH3:14])[CH2:12][O:11][C@H:10]([CH3:15])[CH2:9]2)[N:5]=[C:4]([NH:16][CH3:17])[N:3]=1.[F:18][C:19]1[CH:26]=[C:25](B2OC(C)(C)C(C)(C)O2)[CH:24]=[CH:23][C:20]=1[C:21]#[N:22].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>[CH3:15][C@H:10]1[O:11][CH2:12][C@@H:13]([CH3:14])[N:8]([C:6]2[N:5]=[C:4]([NH:16][CH3:17])[N:3]=[C:2]([C:25]3[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[C:19]([F:18])[CH:26]=3)[CH:7]=2)[CH2:9]1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 513509512-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrileHCID 58504473HCID 58504473, compound

Product 1

HCID 58504450HCID 58504450, compoundYield 55.1%

Reagents, catalysts & solvents 3

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

Procedure

To a solution of 4-chloro-6-[(2R,5R)-2,5-dimethyl-4-morpholinyl]-N-methyl-2-pyrimidinamine (430 mg, 1.675 mmol) and 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (621 mg, 2.51 mmol) in 1,4-dioxane (2 mL) and water (1.00 mL) in a microwave reaction vessel stirred under nitrogen at room temperature was added Na2CO3 (355 mg, 3.35 mmol) and Pd(Ph3P)4 (194 mg, 0.167 mmol). The reaction vessel was sealed and heated in Biotage Initiator using initial normal to 120° C. for 1 hour. After cooling the reaction to room temperature, the mixture was filtered through a pad of celite, and the filter cake was washed with THF (3×30 mL) and CH3OH (3×30 mL). The filtrate was purified with a silica gel (300-400) column and was eluted with Hex/EtOAc (2:1 to 1:2) to afford the title compound (315 mg) as a light yellow solid. LC-MS (ES) m/z=342 [M+H]+.

Workup

  1. customThe reaction vessel was sealed
  2. temperatureheated in Biotage Initiator
  3. customnormal to 120° C.
  4. customfor 1 hour
  5. temperatureAfter cooling
  6. customthe reaction to room temperature
  7. filtrationthe mixture was filtered through a pad of celite
  8. washthe filter cake was washed with THF (3×30 mL) and CH3OH (3×30 mL)
  9. customThe filtrate was purified with a silica gel (300-400) column
  10. washwas eluted with Hex/EtOAc (2:1 to 1:2)

Sources & evidence

ORD record
ord-76f65d1089d045b9a9fcb979671ce422
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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