2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 89615759, compound

HRID 882163Notes

Reaction equation

HRID 882163 reaction equation
Br[C:2]1[C:10]2[C:9]([C:11]3[CH:12]=[C:13]([NH:17][C:18](=[O:22])[C:19]([CH3:21])=[CH2:20])[CH:14]=[CH:15][CH:16]=3)=[N:8][CH:7]=[N:6][C:5]=2[N:4]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[CH:3]=1.C([Sn](CCCC)(CCCC)[C:36]1[O:37][CH:38]=[CH:39][N:40]=1)CCC.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[O:37]1[CH:38]=[CH:39][N:40]=[C:36]1[C:2]1[C:10]2[C:9]([C:11]3[CH:12]=[C:13]([NH:17][C:18](=[O:22])[C:19]([CH3:21])=[CH2:20])[CH:14]=[CH:15][CH:16]=3)=[N:8][CH:7]=[N:6][C:5]=2[N:4]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:28])([CH3:29])[CH3:30])[CH:3]=1

Participants

6

Reactant 3

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 154861832-(Tri-n-butylstannyl)oxazoleHCID 89629894HCID 89629894, compound

Product 1

HCID 89615759HCID 89615759, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of N-(3-(5-bromo-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl)methacrylamide (249 mg, 0.51 mmol) in toluene (10 mL) under nitrogen, was added 2-(tributylstannyl)-1,3-oxazole (548 mg, 1.53 mmol), Pd2(dba)3 (93 mg, 0.10 mmol), and X-Phos (95 mg, 0.20 mmol). The resulting solution was stirred overnight at 60° C. and then concentrated in vacuo, and the resulting crude reaction was extracted with ethyl acetate (×3). The combined organic layers were washed with brine, dried with anhydrous sodium sulfate, filtered and concentrated in vacuo. The reaction was then purified by chromatography using silica gel, eluting with 0-100% EtOAc/petroleum ether. The product was collected and concentrated in vacuo to afford N-(3-(5-(oxazol-2-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl)methacrylamide as a yellow oil. LRMS (ESI) calc'd for C25H30N5O3Si [M+H]+: 476, found 476.

Workup

  1. concentrationconcentrated in vacuo
  2. customthe resulting crude reaction
  3. extractionwas extracted with ethyl acetate (×3)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried with anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe reaction was then purified by chromatography
  9. washeluting with 0-100% EtOAc/petroleum ether
  10. customThe product was collected
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-357415ecf4b742b48a902b8cc1bd56e3
Source dataset
uspto-grants-2015_03
Patent number
US08993756B2

Reaction notes

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