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

HRID 331119

반응식

HRID 331119 반응식
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

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매HCID 8857Ethyl Acetate용매

반응 조건

온도
50 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-e040b9e6303641d8b2290f8e35202707
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08877769B2

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