Dichloromethane → HCID 58504430, compound

HRID 2367544Notes

Reaction equation

HRID 2367544 reaction equation
FC(F)(F)S(O[C:7]1[CH:12]=[C:11]([C:13]2[CH:18]=[C:17]([N:19]3[CH2:24][CH2:23][O:22][CH2:21][C@H:20]3[CH3:25])[N:16]=[C:15]([NH:26][CH3:27])[N:14]=2)[CH:10]=[C:9]([F:28])[C:8]=1[C:29]#[N:30])(=O)=O.[O:33]1[CH:37]=[CH:36][CH:35]=[C:34]1B(O)O.C(Cl)Cl.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.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:28][C:9]1[CH:10]=[C:11]([C:13]2[CH:18]=[C:17]([N:19]3[CH2:24][CH2:23][O:22][CH2:21][C@H:20]3[CH3:25])[N:16]=[C:15]([NH:26][CH3:27])[N:14]=2)[CH:12]=[C:7]([C:34]2[O:33][CH:37]=[CH:36][CH:35]=2)[C:8]=1[C:29]#[N:30]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 2734357Furan-2-boronic acidHCID 58504773HCID 58504773, compound

Product 1

HCID 58504430HCID 58504430, compoundYield 23.9%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Procedure

A solution of 2-cyano-3-fluoro-5-{2-(methylamino)-6-[(3R)-3-methyl-4-morpholinyl]-4-pyrimidinyl}phenyl trifluoromethanesulfonate (374 mg, 0.786 mmol), 2-furanylboronic acid (176 mg, 1.572 mmol), PdCl2(dppf).CH2Cl2 adduct (32.1 mg, 0.039 mmol), and K3PO4 (500 mg, 2.358 mmol) in 1,4-dioxane (10 mL) was heated overnight at 100° C. in a sealed tube. The reaction mixture was allowed to cool, then was partitioned between EtOAc (50 mL) and water (50 mL). The aqueous layer was neutralized with 0.1 M HCl (pH paper) and extracted with EtOAc (3×50 mL). The combined organics were dried over Na2SO4, and concentrated. The residue was purified by RP-HPLC (15-50% CH3CN in water, 0.1% TFA). The product fractions were combined, basified with NaHCO3, extracted with EtOAc, dried, and concentrated to afford the title compound (74 mg) as a brown solid LC-MS (ES) m/z=394 [M+H]+.

Workup

  1. temperatureto cool
  2. customwas partitioned between EtOAc (50 mL) and water (50 mL)
  3. extractionextracted with EtOAc (3×50 mL)
  4. dry with materialThe combined organics were dried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by RP-HPLC (15-50% CH3CN in water, 0.1% TFA)
  7. extractionextracted with EtOAc
  8. customdried
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-951987befe964189be1b0eae90e93dfc
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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