3-Bromoaniline → Ethyl 4-[(3-bromophenyl)amino]-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidine-7-carboxylate

HRID 1292953Notes

Reaction equation

HRID 1292953 reaction equation
[CH2:1]([O:3][C:4]([CH:6]1[CH2:19][CH2:18][C:9]2[C:10]3[C:15](Cl)=[N:14][CH:13]=[N:12][C:11]=3[S:17][C:8]=2[CH2:7]1)=[O:5])[CH3:2].[Br:20][C:21]1[CH:22]=[C:23]([CH:25]=[CH:26][CH:27]=1)[NH2:24]>C(O)C.Cl>[Br:20][C:21]1[CH:22]=[C:23]([NH:24][C:15]2[C:10]3[C:9]4[CH2:18][CH2:19][CH:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH2:7][C:8]=4[S:17][C:11]=3[N:12]=[CH:13][N:14]=2)[CH:25]=[CH:26][CH:27]=1

Participants

5

Reactant 2

HCID 115623-BromoanilineHCID 17990004Ethyl 4-chloro-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine-7-carboxylate

Product 1

HCID 17990000Ethyl 4-[(3-bromophenyl)amino]-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidine-7-carboxylateYield 77.2%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

In a 25 mL round-bottom flask were placed 250 mg (0.84 mmol, 1.1 equiv) of 4-chloro-5,6,7,8-tetrahydro-benzo[4,5]thieno[2,3-d]pyrimidine-7-carboxylic acid ethyl ester and 131 mg (0.77 mmol, 1 equiv) m-bromoaniline in 10 mL of ethanol with one drop conc HCl. The flask was equipped with a reflux condenser and heated at 70° C. for 4 h. The mixture was allowed to cool to rt and ethanol was concentrated in vacuo. The resulting crude residue was re-dissolved in EtOAc (10 mL), poured into a separatory funnel and washed with satd NaHCO3 (1×10 mL). The organic layer was dried (MgSO4), filtered and concentrated to give a crude oil. The crude material was further purified by MPLC (Biotage) using 1/4 EtOAc/Hex to provide 257 mg (77%) of the desired product, 14, as a white powder. 1H-NMR (CDCl3-d) δ 8.44 (s, 1H), 7.92 (s, 1H), 7.55 (m, 1H), 7.23 (m, 2H), 7.08 (s, 1H), 4.22 (q, 2H), 3.14 (m, 4H), 2.91 (m, 1H), 2.39 (m, 1H), 2.14 (m, 1H), 1.30 (t, 3H); LCMS RT=3.48 min; [M+H]+=432.

Workup

  1. customIn a 25 mL round-bottom flask were placed
  2. customThe flask was equipped with a reflux condenser
  3. temperatureto cool to rt
  4. concentrationethanol was concentrated in vacuo
  5. dissolutionThe resulting crude residue was re-dissolved in EtOAc (10 mL)
  6. additionpoured into a separatory funnel
  7. washwashed with satd NaHCO3 (1×10 mL)
  8. dry with materialThe organic layer was dried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give a crude oil
  12. customThe crude material was further purified by MPLC (Biotage)

Sources & evidence

ORD record
ord-8a563db5330d4a93b102dcc1d57c1228
Source dataset
uspto-grants-2007_07
Patent number
US07238701B2

Reaction notes

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