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

HRID 331120

Reaction equation

HRID 331120 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-6dc392e1500b465c86bbd4470253cb27
Source dataset
uspto-grants-2014_11
Patent number
US08877769B2

Linked notes

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