2-Aminobenzoxazole → 4-[3-(4-Chloro-phenoxy)-benzyl]-piperazine-1-carboxylic acid benzooxazol-2-ylamide

HRID 1255777Notes

Reaction equation

HRID 1255777 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH2:10].C1C(=O)N(OC(ON2C(=O)CCC2=O)=O)[C:13](=[O:14])C1.Cl.[Cl:30][C:31]1[CH:50]=[CH:49][C:34]([O:35][C:36]2[CH:37]=[C:38]([CH:46]=[CH:47][CH:48]=2)[CH2:39][N:40]2[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]2)=[CH:33][CH:32]=1.C(N(C(C)C)CC)(C)C>C(Cl)Cl.CCOC(C)=O>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:13]([N:43]1[CH2:44][CH2:45][N:40]([CH2:39][C:38]2[CH:46]=[CH:47][CH:48]=[C:36]([O:35][C:34]3[CH:49]=[CH:50][C:31]([Cl:30])=[CH:32][CH:33]=3)[CH:37]=2)[CH2:41][CH2:42]1)=[O:14]

Participants

7

Reactant 4

HCID 207072-AminobenzoxazoleHCID 81531DiisopropylethylamineHCID 676246Di(succinimido) carbonateHCID 674138091-[3-(4-Chloro-phenoxy)-benzyl]-piperazine hydrochloride

Product 1

HCID 462343144-[3-(4-Chloro-phenoxy)-benzyl]-piperazine-1-carboxylic acid benzooxazol-2-ylamideYield 63.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of benzooxazole-2-ylamine (35.8 mg, 0.267 mmol) in CH2Cl2 (6.0 mL) was added N,N′-disuccinimidyl carbonate (68.4 mg, 0.267 mmol). The reaction mixture was stirred at rt for 6 h, then treated with 1-[3-(4-chloro-phenoxy)-benzyl]-piperazine hydrochloride (100 mg, 0.267 mmol) and diisopropylethylamine (92 μL, 0.536 mmol) and stirred for an additional 16 h at rt. The reaction mixture was diluted with EtOAc (100 mL) and extracted with H2O (100 mL) then saturated aqueous NaCl (50 mL). The organic layer was dried (MgSO4), and concentrated. The crude residue was purified (FCC, 2 N NH3 in MeOH/DCM) to give 4-[3-(4-chloro-phenoxy)-benzyl]-piperazine-1-carboxylic acid benzooxazol-2-ylamide (78.0 mg, 63%). MS (ESI+): calcd for C25H23ClN4O3 m/z 462.15. found 463.5 (M+H)+. 1H NMR (d6-DMSO): 12.13 (br s, 1H), 7.46-7.39 (m, 3H), 7.36 (t, J=7.9, 1H), 7.30 (br s, 1H), 7.22 (t, J=7.6, 1H), 7.18-7.11 (m, 2H), 7.04 (d, J=9.0, 2H), 7.00 (br s, 1H), 6.94-6.91 (m, 1H), 3.73-3.54 (br m, 4H), 3.50 (s, 2H), 2.40-2.31 (m, 4H).

Workup

  1. stirringstirred for an additional 16 h at rt
  2. extractionextracted with H2O (100 mL)
  3. dry with materialThe organic layer was dried (MgSO4)
  4. concentrationconcentrated
  5. customThe crude residue was purified (FCC, 2 N NH3 in MeOH/DCM)

Sources & evidence

ORD record
ord-41ab6fef697b41a6b0243be01bec99a8
Source dataset
uspto-grants-2013_06
Patent number
US08461159B2

Reaction notes

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