Propylphosphonic anhydride → Ethyl 4-(3-{[2-({[tert-butyl(dimethyl)silyl]oxy}methyl)acryloyl]amino}phenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate

HRID 882145Notes

Reaction equation

HRID 882145 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([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:5]=[CH:6][CH:7]=1.[Si:22]([O:29][CH2:30][C:31](=[CH2:35])[C:32](O)=[O:33])([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23].CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>O1CCCC1>[Si:22]([O:29][CH2:30][C:31](=[CH2:35])[C:32]([NH:1][C:2]1[CH:3]=[C:4]([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:5]=[CH:6][CH:7]=1)=[O:33])([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:23])[CH3:24]

Participants

5

Reactant 3

HCID 111923Propylphosphonic anhydrideHCID 446042572-(((tert-Butyldimethylsilyl)oxy)methyl)acrylic acidHCID 71598790ethyl 4-(3-aminophenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate

Product 1

HCID 89613801Ethyl 4-(3-{[2-({[tert-butyl(dimethyl)silyl]oxy}methyl)acryloyl]amino}phenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

To ethyl 4-(3-aminophenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate (80 mg, 0.28 mmol) was added tetrahydrofuran (2.8 mL), TEA (59.2 μL, 0.425 mmol), 2-({[tert-butyl(dimethyl)silyl]oxy}methyl)prop-2-enoic acid (80 mg, 0.37 mmol) and 1-propanephosphonic acid cyclic anhydride (169 μL, 0.283 mmol). The reaction was stirred at 25° C. overnight before being quenched by pouring into a separatory funnel containing aqueous sodium bicarbonate (5%). The solution was extracted with ethyl acetate (×3) and the organic layers were combined and dried with Na2SO4, filtered, and concentrated in vacuo. The crude product was then purified by silica chromatography by MPLC using 1-8% CH2Cl2MeOH. Concentration of the desired fractions afforded the title compound as a colorless solid. LRMS (ESI) calc'd for C25H33N4O4Si [M+H]+, 481; found 481.

Workup

  1. custombefore being quenched
  2. additionby pouring into a separatory funnel
  3. additioncontaining aqueous sodium bicarbonate (5%)
  4. extractionThe solution was extracted with ethyl acetate (×3)
  5. dry with materialdried with Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was then purified by silica chromatography by MPLC

Sources & evidence

ORD record
ord-c587eec807cf4852b8f5f2408cb30fa4
Source dataset
uspto-grants-2015_03
Patent number
US08993756B2

Reaction notes

Loading…