Diisopropylethylamine → 4-[3-(4-Chloro-phenoxy)-benzyl]-piperazine-1-carboxylic acid imidazo[1,2-b]pyridazin-3-ylamide

HRID 1255776Notes

Reaction equation

HRID 1255776 reaction equation
Cl.[Cl:2][C:3]1[CH:22]=[CH:21][C:6]([O:7][C:8]2[CH:9]=[C:10]([CH:18]=[CH:19][CH:20]=2)[CH2:11][N:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)=[CH:5][CH:4]=1.C(N(C(C)C)CC)(C)C.C1([O:38][C:39](=O)[NH:40][C:41]2[N:45]3[N:46]=[CH:47][CH:48]=[CH:49][C:44]3=[N:43][CH:42]=2)C=CC=CC=1>CS(C)=O.CCOC(C)=O>[N:43]1[CH:42]=[C:41]([NH:40][C:39]([N:15]2[CH2:16][CH2:17][N:12]([CH2:11][C:10]3[CH:18]=[CH:19][CH:20]=[C:8]([O:7][C:6]4[CH:21]=[CH:22][C:3]([Cl:2])=[CH:4][CH:5]=4)[CH:9]=3)[CH2:13][CH2:14]2)=[O:38])[N:45]2[C:44]=1[CH:49]=[CH:48][CH:47]=[N:46]2

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 58442681Imidazo[1,2-b]pyridazin-3-yl-carbamic acid phenyl esterHCID 674138091-[3-(4-Chloro-phenoxy)-benzyl]-piperazine hydrochloride

Product 1

HCID 462139484-[3-(4-Chloro-phenoxy)-benzyl]-piperazine-1-carboxylic acid imidazo[1,2-b]pyridazin-3-ylamideYield 87.3%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 1-[3-(4-chloro-phenoxy)-benzyl]-piperazine hydrochloride (62.3 mg, 0.166 mmol) and diisopropylethylamine (53.7 mg, 0.416 mmol) in DMSO (2.0 mL) was added imidazo[1,2-b]pyridazin-3-yl-carbamic acid phenyl ester (42.1 mg, 0.166 mmol). The reaction mixture was stirred at 50° C. for 16 h, then diluted with EtOAc (40 mL) and washed with saturated aqueous NaHCO3 (40 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 imidazo[1,2-b]pyridazin-3-ylamide (67.1 mg, 87%). MS (ESI+): calcd for C24H23ClN6O2 m/z 462.16. found 463.5 (M+H)+. 1H NMR (d6-DMSO): 8.74 (s, 1H), 8.50 (dd, J=4.4, 1.3, 1H), 8.05 (dd, J=9.1, 1.3, 1H), 7.64 (s, 1H), 7.44 (d, J=9.0, 2H), 7.38 (t, J=7.8, 1H), 7.19-7.12 (m, 2H), 7.04 (d, J=9.0, 2H), 7.01 (br s, 1H), 6.95-6.92 (m, 1H), 3.53 (s, 2H), 3.50-3.45 (m, 4H), 2.43-2.37 (m, 4H).

Workup

  1. washwashed with saturated aqueous NaHCO3 (40 mL)
  2. dry with materialThe organic layer was dried (MgSO4)
  3. concentrationconcentrated
  4. customThe crude residue was purified (FCC, 2 N NH3 in MeOH/DCM)

Sources & evidence

ORD record
ord-82c01010e02a4347a80a02299c9d009c
Source dataset
uspto-grants-2013_06
Patent number
US08461159B2

Reaction notes

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