Diisopropylethylamine → 2-(1,3-Thiazol-4-yl)-1H-benzimidazol-6-amine

HRID 1437825Notes

Reaction equation

HRID 1437825 reaction equation
C(OC(=O)[NH:7][C:8]1[CH:13]=[CH:12][C:11]([NH2:14])=[C:10]([N+:15]([O-])=O)[CH:9]=1)(C)(C)C.[S:19]1[CH:23]=[C:22]([C:24](O)=O)[N:21]=[CH:20]1.C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1>CN(C)C=O>[S:19]1[CH:23]=[C:22]([C:24]2[NH:15][C:10]3[CH:9]=[C:8]([NH2:7])[CH:13]=[CH:12][C:11]=3[N:14]=2)[N:21]=[CH:20]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 3042714-Thiazolecarboxylic acidHCID 2724699PyBOPHCID 16216773CarbaMic acid, N-(4-aMino-3-nitrophenyl)-, 1,1-diMethylethyl ester

Product 1

HCID 1349122-(1,3-Thiazol-4-yl)-1H-benzimidazol-6-amine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of (4-Amino-3-nitro-phenyl)-carbamic acid tert-butyl ester (1-3, 0.409 g, 1.832 mmol), thiazole 4-carboxylic acid (0.226 g, 1.832 mmol) and diisopropylethylamine (0.81 mL, 4.03 mmol) in N,N-dimethylformamide (10 mL) was reacted at the ambient temperature with benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate (PyBop, 1.05 g, 2.02 mmmol). After 3 h stirring at the same temperature, the reaction mixture was concentrated under the reduced pressure and the residue was partitioned between ethyl acetate (100 mL) and aqueous 0.5N-NaOH solution (70 mL). The organic layer was washed with brine, separated, dried (MgSO4) and concentrated in vacuo. The resulting crude product was triturated with ethyl acetate (5 mL), collected by filtration, and dried under the reduced pressure. The mixture of the intermediate products (1-4a and 1-4b) was dissolved in aqueous 20%(v/v)-acetic acid (50 mL) and heated at reflux for 2 h. The reaction mixture was cooled to the ambient temperature and concentrated in vacuo. The resulting crude thick oil was partitioned between ethyl acetate (100 mL) and saturated aqueous sodium bicarbonate solution (70 mL). The organic layer was washed with brine, separated, dried (MgSO4) and concentrated in vacuo. The crude product was triturated with ethyl acetate (15 mL) and hexanes (2 mL). The resulting solid, 2-thiazol-4-yl-3H-benzoimidazol-5-ylamine (1-5), was collected by filtration and dried under the reduced pressure; 1H NMR (500 MHz, DMSO-d6) δ 12.34 (s, 1H), 9.27 (s, 1H), 8.24 (s, 1H), 7.27 (bs, 1H), 6.66 (s, 1H), 6.54 (d, 1H, J=7.5 Hz), 4.96 (bs, 2H).

Workup

  1. concentrationthe reaction mixture was concentrated under the reduced pressure
  2. customthe residue was partitioned between ethyl acetate (100 mL) and aqueous 0.5N-NaOH solution (70 mL)
  3. washThe organic layer was washed with brine
  4. customseparated
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe resulting crude product was triturated with ethyl acetate (5 mL)
  8. filtrationcollected by filtration
  9. customdried under the reduced pressure
  10. additionThe mixture of the intermediate products (1-4a and 1-4b)
  11. dissolutionwas dissolved in aqueous 20%(v/v)-acetic acid (50 mL)
  12. temperatureheated
  13. temperatureat reflux for 2 h
  14. concentrationconcentrated in vacuo
  15. customThe resulting crude thick oil was partitioned between ethyl acetate (100 mL) and saturated aqueous sodium bicarbonate solution (70 mL)
  16. washThe organic layer was washed with brine
  17. customseparated
  18. dry with materialdried (MgSO4)
  19. concentrationconcentrated in vacuo
  20. customThe crude product was triturated with ethyl acetate (15 mL) and hexanes (2 mL)
  21. filtrationThe resulting solid, 2-thiazol-4-yl-3H-benzoimidazol-5-ylamine (1-5), was collected by filtration
  22. customdried under the reduced pressure

Sources & evidence

ORD record
ord-a95fb10750c1495b99be1477392e52ef
Source dataset
uspto-grants-2009_11
Patent number
US07622592B2

Reaction notes

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