Sodium Carbonate → cis-2-[2-(2,6-Dimethyl-4-morpholinyl)-5-(2-methyl-4-pyridinyl)-4-pyrimidinyl]-6-(trifluoromethyl)benzonitrile hydrochloride

HRID 2278457Notes

Reaction equation

HRID 2278457 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].CC1(C)COB([C:14]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([F:25])([F:24])[F:23])[C:15]=2[C:16]#[N:17])OC1.[Cl:27][C:28]1[C:33]([C:34]2[CH:39]=[CH:38][N:37]=[C:36]([CH3:40])[CH:35]=2)=[CH:32][N:31]=[C:30]([N:41]2[CH2:46][C@H:45]([CH3:47])[O:44][C@H:43]([CH3:48])[CH2:42]2)[N:29]=1>O.COCCOC.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[ClH:27].[CH3:47][C@H:45]1[O:44][C@@H:43]([CH3:48])[CH2:42][N:41]([C:30]2[N:31]=[C:32]([C:14]3[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([F:23])([F:24])[F:25])[C:15]=3[C:16]#[N:17])[C:33]([C:34]3[CH:39]=[CH:38][N:37]=[C:36]([CH3:40])[CH:35]=3)=[CH:28][N:29]=2)[CH2:46]1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 116233352-(5,5-Dimethyl-1,3,2-dioxaborinan-2-yl)-6-(trifluoromethyl)benzonitrileHCID 86702425cis-4-(4-Chloro-5-(2-methylpyridin-4-yl)pyrimidin-2-yl)-2,6-dimethylmorpholine

Product 1

HCID 86702435cis-2-[2-(2,6-Dimethyl-4-morpholinyl)-5-(2-methyl-4-pyridinyl)-4-pyrimidinyl]-6-(trifluoromethyl)benzonitrile hydrochlorideYield 48.8%

Reagents, catalysts & solvents 3

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

Sodium carbonate (166 mg, 1.568 mmol) in water (2 mL), bis(triphenylphosphine) palladium(II) chloride (11.01 mg, 0.016 mmol) and 2-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-6-(trifluoromethyl)benzonitrile (178 mg, 0.627 mmol) were added to a solution of cis-4-[4-chloro-5-(2-methyl-4-pyridinyl)-2-pyrimidinyl]-2,6-dimethylmorpholine (100 mg, 0.314 mmol) in 1,2-dimethoxyethane (3 mL). The reaction mixture was heated to 100° C. for 2 hours. The reaction mixture diluted with water (5 mL) and extracted with DCM (5 mL×2). The organic extracts were combined, dried (MgSO4), filtered and the solvent was removed. The resulting residues were then purified by MDAP and fractions containing desired product were combined and evaporated to dryness. The solid was dissolved in methanol (2 mL) and 4M HCl in dioxane (1 mL) was added. The solvent was removed to give the title compound (75 mg). LC/MS [M+H]+=454.

Workup

  1. extractionextracted with DCM (5 mL×2)
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. customthe solvent was removed
  5. customThe resulting residues were then purified by MDAP and fractions
  6. additioncontaining desired product
  7. customevaporated to dryness
  8. dissolutionThe solid was dissolved in methanol (2 mL)
  9. addition4M HCl in dioxane (1 mL) was added
  10. customThe solvent was removed

Sources & evidence

ORD record
ord-10b17b55eade4ffc9d6640b205e451cd
Source dataset
uspto-grants-2015_09
Patent number
US09133178B2

Reaction notes

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