Sodium Bicarbonate → HCID 58504530, compound

HRID 2367612Notes

Reaction equation

HRID 2367612 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[C:26]([F:27])=[CH:25][C:24](B(O)O)=[CH:23][C:22]=1[F:31])#[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:27][C:26]1[CH:25]=[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:23]=[C:22]([F:31])[C:21]=1[C:19]#[N:20]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 55252910(4-Cyano-3,5-difluorophenyl)boronic acidHCID 58504551HCID 58504551, compound

Product 1

HCID 58504530HCID 58504530, compoundYield 55.2%

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 (600 mg, 2.138 mmol) and (4-cyano-3,5-difluorophenyl)boronic acid (587 mg, 3.21 mmol) were dissolved in 1,4-dioxane (10 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 50 g column with a gradient of 0 to 35% EtOAc in Hexane over 30 minutes to isolated the title compound (452 mg). LC-MS (ES) m/z=384 [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 50 g column with a gradient of 0 to 35% EtOAc in Hexane over 30 minutes

Sources & evidence

ORD record
ord-171e75af808a4e72bb7e8060683d03b4
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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