Methacrylic Acid → HCID 71599508, compound

HRID 882125Notes

Reaction equation

HRID 882125 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([F:22])=[C:6]([C:8]2[C:9]3[C:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:15][NH:14][C:10]=3[N:11]=[CH:12][N:13]=2)[CH:7]=1.[CH3:23][C:24](=[CH2:28])[C:25](O)=[O:26].CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>C1COCC1>[F:22][C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:25](=[O:26])[C:24]([CH3:28])=[CH2:23])=[CH:7][C:6]=1[C:8]1[C:9]2[C:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:15][NH:14][C:10]=2[N:11]=[CH:12][N:13]=1

Participants

5

Reactant 3

HCID 4093Methacrylic AcidHCID 111923Propylphosphonic anhydrideHCID 71599681HCID 71599681, compound

Product 1

HCID 71599508HCID 71599508, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

To crude ethyl 4-(5-amino-2-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate (133 mg, 0.443 mmol) was added THF (4.43 mL), TEA (93 μL, 0.66 mmol), methylacrylic acid (57 mg, 0.66 mmol) and 1-propanephosphonic acid cyclic anhydride (3.26 mL, 0.443 mmol). The reaction was stirred at 25° C. overnight. The reaction was quenched by pouring into a separatory funnel containing aqueous sodium hydrogen carbonate (5%) and was extracted with ethyl acetate (×3). The organic layers were combined and dried with Na2SO4, filtered, and evaporated in vacuo. The crude reaction was purified by reverse phase HPLC using an acetonitrile gradient in water with 0.1% TFA modifier. The products were collected and lyophilized to afford a colorless solid. LRMS (ESI) calc'd for C19H18N4O3F [M+H]+: 369, found 369.

Workup

  1. customThe reaction was quenched
  2. additionby pouring into a separatory funnel
  3. additioncontaining aqueous sodium hydrogen carbonate (5%)
  4. extractionwas extracted with ethyl acetate (×3)
  5. dry with materialdried with Na2SO4
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe crude reaction
  9. customwas purified by reverse phase HPLC
  10. customThe products were collected
  11. customto afford a colorless solid

Sources & evidence

ORD record
ord-bff2166e06d84ea990789477ff7982b0
Source dataset
uspto-grants-2015_03
Patent number
US08993756B2

Reaction notes

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