3-Nitrophenylboronic Acid → ethyl 4-(3-nitrophenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate

HRID 882113Notes

Reaction equation

HRID 882113 reaction equation
Cl[C:2]1[C:3]2[C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[N+:16]([C:19]1[CH:20]=[C:21](B(O)O)[CH:22]=[CH:23][CH:24]=1)([O-:18])=[O:17].C(=O)([O-])[O-].[Na+].[Na+]>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].C(Cl)Cl.CN(C=O)C>[N+:16]([C:19]1[CH:24]=[C:23]([C:2]2[C:3]3[C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:9][NH:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:22]=[CH:21][CH:20]=1)([O-:18])=[O:17]

Participants

6

Reactant 3

HCID 16773-Nitrophenylboronic AcidHCID 10340Sodium CarbonateHCID 105611797H-Pyrrolo(2,3-d)pyrimidine-5-carboxylic acid, 4-chloro-, ethyl ester

Product 1

HCID 117703162ethyl 4-(3-nitrophenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
115 °C

Procedure

To ethyl 4-chloro-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate (10.0 g, 44.3 mmol), (3-nitrophenyl)boronic acid (11.8 g, 70.9 mmol), PdCl2(dppf)-CH2Cl2 (3.62 g, 4.43 mmol) and aqueous sodium carbonate (2 M solution, 55.4 mL, 111 mmol) in a flask was added DMF (148 mL). The mixture was degassed for 10 minutes then heated at 115° C. for 1.5 hours. The reaction was cooled to ambient temperature, then water was added and the mixture was extracted with DCM (×3) and EtOAc (×1). The combined organics were concentrated, diluted with EtOAc (300 mL) and washed with sorbitol/Na2CO3 solution to remove excess boronic acid. The aqueous layer was extracted with EtOAc (×4). The combined organics were concentrated after which EtOAc and hexanes were added with stirring. The resulting precipitate was filtered to give solid product that was further triturated with DCM and hexanes to give ethyl 4-(3-nitrophenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate. The combined organic fractions were concentrated under reduced pressure to give a residue containing product and DMF. Addition of MeOH and water led to formation of a precipitate which was filtered to afford additional ethyl 4-(3-nitrophenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate. LRMS (ESI) calc'd for C15H13N4O4 [M+H]+: 313, found 313. 1H NMR (600 MHz, DMSO-D6) δ 13.17 (s, 1H), 8.99 (s, 1H), 8.43 (s, 1H), 8.39-8.36 (m, 2H), 8.12 (d, J=7.8 Hz, 1H), 7.79 (t, J=7.8 Hz, 1H), 3.93 (q, J=7.2 Hz, 2H), 0.95 (t, J=7.2 Hz, 3H).

Workup

  1. customThe mixture was degassed for 10 minutes
  2. temperatureThe reaction was cooled to ambient temperature
  3. additionwater was added
  4. extractionthe mixture was extracted with DCM (×3) and EtOAc (×1)
  5. concentrationThe combined organics were concentrated
  6. additiondiluted with EtOAc (300 mL)
  7. washwashed with sorbitol/Na2CO3 solution
  8. customto remove excess boronic acid
  9. extractionThe aqueous layer was extracted with EtOAc (×4)
  10. concentrationThe combined organics were concentrated after which EtOAc and hexanes
  11. additionwere added
  12. filtrationThe resulting precipitate was filtered
  13. customto give solid product that
  14. customwas further triturated with DCM and hexanes

Sources & evidence

ORD record
ord-b26f0833e6db485bbdea601a8fa19dd9
Source dataset
uspto-grants-2015_03
Patent number
US08993756B2

Reaction notes

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