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

HRID 331119

反応式

HRID 331119 の反応式
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

参加物

6

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
50 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-e040b9e6303641d8b2290f8e35202707
出典データセット
uspto-grants-2014_11
特許番号
US08877769B2

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