4-Bromophenyl isothiocyanate → Tert-butyl 4-{2-[(4-bromophenyl)amino]-1-methylbenzimidazol-5-yloxy}pyridine-2-carboxylate

HRID 13448

Reaction equation

HRID 13448 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[NH:22][CH3:23])[O:5][C:6]1[CH:11]=[CH:10][N:9]=[C:8]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH:7]=1.[Br:24][C:25]1[CH:30]=[CH:29][C:28]([N:31]=[C:32]=S)=[CH:27][CH:26]=1.Cl.C(N=C=NCCCN(C)C)C>O1CCCC1>[Br:24][C:25]1[CH:30]=[CH:29][C:28]([NH:31][C:32]2[N:22]([CH3:23])[C:21]3[CH:20]=[CH:19][C:4]([O:5][C:6]4[CH:11]=[CH:10][N:9]=[C:8]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH:7]=4)=[CH:3][C:2]=3[N:1]=2)=[CH:27][CH:26]=1

Participants

5

Reactant 3

HCID 161334-Bromophenyl isothiocyanateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22040526Tert-butyl4-[3-amino-4-(methylamino)phenoxy]pyridine-2-carboxylate

Product 1

HCID 22041284Tert-butyl 4-{2-[(4-bromophenyl)amino]-1-methylbenzimidazol-5-yloxy}pyridine-2-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A solution of the diamine from step 6 (1 eq) and 4-bromophenyl isothiocyanate (1 eq) in anhydrous tetrahydrofuran under nitrogen was stirred at 20° C. for 2-3 hours or when determined to be complete by HPLC. The solution was treated with 3 equivalents of 1-ethyl-(3-dimethylaminopropyl)carbodiimide HCl. The stirred solution was heated to 50° C. under nitrogen for 2-3 hrs or until the reaction is determined to be complete by HPLC. The reaction was evaporated under reduced pressure and then diluted with ethyl acetate and water. The aqueous layer was back extracted with ethyl acetate. The combined organic layers were washed with water and brine. The organic layer was dried over anhydrous sodium sulfate and later evaporated under reduced pressure. The crude material was purified by reverse high-pressure liquid chromatography to afford the product as a brown powder after lyophlization. MS: MH+=495.

Workup

  1. customThe reaction was evaporated under reduced pressure
  2. additiondiluted with ethyl acetate and water
  3. extractionThe aqueous layer was back extracted with ethyl acetate
  4. washThe combined organic layers were washed with water and brine
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. customlater evaporated under reduced pressure
  7. customThe crude material was purified

Sources & evidence

ORD record
ord-60b69ec45ef5433382901702972b2df1
Source dataset
uspto-grants-2010_06
Patent number
US07728010B2

Linked notes

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