Sodium Bicarbonate → HCID 58504437, compound

HRID 2367615Notes

Reaction equation

HRID 2367615 reaction equation
Cl[C:2]1[CH:7]=[C:6]([N:8]2[CH2:12][CH2:11][CH2:10][C@H:9]2[C:13]([F:16])([F:15])[F:14])[N:5]=[C:4]([NH:17][CH3:18])[N:3]=1.[C:19]([C:21]1[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][C:22]=1[F:30])#[N:20].C([O-])(O)=O.[Na+]>O1CCOCC1.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>[F:30][C:22]1[CH:23]=[C:24]([C:2]2[CH:7]=[C:6]([N:8]3[CH2:12][CH2:11][CH2:10][C@H:9]3[C:13]([F:16])([F:15])[F:14])[N:5]=[C:4]([NH:17][CH3:18])[N:3]=2)[CH:25]=[CH:26][C:21]=1[C:19]#[N:20]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 2783130(4-Cyano-3-fluorophenyl)boronic acidHCID 58504551HCID 58504551, compound

Product 1

HCID 58504437HCID 58504437, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

4-Chloro-N-methyl-6-[(2S)-2-(trifluoromethyl)-1-pyrrolidinyl]-2-pyrimidinamine (110 mg, 0.392 mmol) and (4-cyano-3-fluorophenyl)boronic acid (97 mg, 0.588 mmol) were dissolved in 1,4-dioxane (4 mL) in a 20 mL sealable vial. Saturated NaHCO3 solution (5 mL) was added, and N2 gas was bubbled through the mixture for 10 minutes. Then Pd(Ph3P)4 (371 mg, 0.321 mmol) was added, and N2 gas was bubbled through the mixture for an additional 5 minutes. The reaction vial was then capped and heated at 100° C. overnight. The reaction was diluted with water (10 mL) and then extracted with EtOAc (3×10 mL). Organic was then combined, dried over MgSO4, filtered and concentrated. The yellow oil was then purified on Biotage SNAP 10 g column with a gradient of 0 to 35% EtOAc in Hexane for 30 minutes to afford the title compouns (167 mg). LC-MS (ES) m/z=366 [M+H]+.

Workup

  1. customN2 gas was bubbled through the mixture for 10 minutes
  2. customN2 gas was bubbled through the mixture for an additional 5 minutes
  3. customThe reaction vial was then capped
  4. additionThe reaction was diluted with water (10 mL)
  5. extractionextracted with EtOAc (3×10 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe yellow oil was then purified on Biotage SNAP 10 g column with a gradient of 0 to 35% EtOAc in Hexane for 30 minutes
  10. customto afford the title compouns (167 mg)

Sources & evidence

ORD record
ord-64fb691a871c4c90a3b1f9975d317034
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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