Acetonitrile → HCID 44538978, compound

HRID 1639582Notes

Reaction equation

HRID 1639582 reaction equation
Br[C:2]1[N:3]=[C:4]2[C:10]([C:11]([C:13]3[C:14]([F:27])=[C:15]([NH:20][S:21]([CH2:24][CH2:25][CH3:26])(=[O:23])=[O:22])[CH:16]=[CH:17][C:18]=3[F:19])=[O:12])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[CH3:28][O:29][C:30]1[N:35]=[CH:34][C:33](B(O)O)=[CH:32][N:31]=1.C(#N)C.C(=O)([O-])[O-].[K+].[K+]>O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:27][C:14]1[C:13]([C:11]([C:10]2[C:4]3[C:5](=[N:6][CH:7]=[C:2]([C:33]4[CH:32]=[N:31][C:30]([O:29][CH3:28])=[N:35][CH:34]=4)[N:3]=3)[NH:8][CH:9]=2)=[O:12])=[C:18]([F:19])[CH:17]=[CH:16][C:15]=1[NH:20][S:21]([CH2:24][CH2:25][CH3:26])(=[O:23])=[O:22]

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 27367782-Methoxypyrimidine-5-boronic acidHCID 44538981HCID 44538981, compound

Product 1

HCID 44538978HCID 44538978, compoundYield 31.6%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Conditions

Temperature
160 °C

Procedure

In a microwave tube, propane-1-sulfonic acid [3-(2-bromo-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl)-2,4-difluoro-phenyl]-amide (P-0002, 95.0 mg, 0.207 mmol) and 2-methoxypyrimidine-5-boronic acid (10, 38.0 mg, 0.247 mmol) were added, followed by 1.4 mL of acetonitrile and 0.70 mL of 1.00 M potassium carbonate in water. [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (7.6 mg, 0.010 mmol) was added to reaction mixture and the resulting mixture was heated at 160° C. in the microwave for a total of 10 minutes. The reaction solution was extracted with ethyl acetate and water, followed by saturated sodium chloride. The organic layer was dried with anhydrous magnesium sulfate, filtered and the filtrate concentrated under vacuum. The crude material was purified by silica gel chromatography eluting with a gradient of 10 to 70% ethyl acetate in hexanes. The resulting material was further purified by silica gel chromatography eluting with a gradient of 1 to 3% methanol in dichloromethane, and fractions containing the desired compound were extracted with 10 mL each of ethyl acetate and 1 M sodium hydroxide. The aqueous layer was treated with 0.8 ml, of 6 N hydrochloric acid, then extracted with 2×10 mL of ethyl acetate. The combined organic layers were dried over anhydrous magnesium sulfate, filtered and the filtrate concentrated under vacuum to provide the desired compound as a white solid (P-0004, 32 mg). MS (ESI) [M+H+]+=489.3.

Workup

  1. extractionThe reaction solution was extracted with ethyl acetate and water
  2. dry with materialThe organic layer was dried with anhydrous magnesium sulfate
  3. filtrationfiltered
  4. concentrationthe filtrate concentrated under vacuum
  5. customThe crude material was purified by silica gel chromatography
  6. washeluting with a gradient of 10 to 70% ethyl acetate in hexanes
  7. customThe resulting material was further purified by silica gel chromatography
  8. washeluting with a gradient of 1 to 3% methanol in dichloromethane, and fractions
  9. additioncontaining the desired compound
  10. extractionwere extracted with 10 mL each of ethyl acetate and 1 M sodium hydroxide
  11. additionThe aqueous layer was treated with 0.8 ml, of 6 N hydrochloric acid
  12. extractionextracted with 2×10 mL of ethyl acetate
  13. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  14. filtrationfiltered
  15. concentrationthe filtrate concentrated under vacuum

Sources & evidence

ORD record
ord-68b2ba9c93824cfe8d15a2e942ecf914
Source dataset
uspto-grants-2012_02
Patent number
US08110576B2

Reaction notes

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