4-Chloro-5-fluoro-1,2-phenylenediamine → 5-Chloro-2-[3-chloro-4-(3-piperazin-1-yl-propoxy)-phenyl]-6-fluoro-1H-benzoimidazole

HRID 2241764

반응식

HRID 2241764 반응식
C(OC([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]3[NH:28][C:27]4[CH:29]=[C:30]([F:34])[C:31]([Cl:33])=[CH:32][C:26]=4[N:25]=3)=[CH:20][C:19]=2[Cl:35])[CH2:10][CH2:9]1)=O)(C)(C)C.C(OC(N1CCN(CCCOC2C=CC(C=O)=CC=2Cl)CC1)=O)(C)(C)C.ClC1C=C(N)C(N)=CC=1F>>[Cl:33][C:31]1[C:30]([F:34])=[CH:29][C:27]2[NH:28][C:24]([C:21]3[CH:22]=[CH:23][C:18]([O:17][CH2:16][CH2:15][CH2:14][N:11]4[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]4)=[C:19]([Cl:35])[CH:20]=3)=[N:25][C:26]=2[CH:32]=1

참가 물질

4

반응물 3

HCID 7357734-Chloro-5-fluoro-1,2-phenylenediamineHCID 575254314-{3-[2-Chloro-4-(5-chloro-6-fluoro-1H-benzoimidazol-2-yl)-phenoxy]-propyl}-piperazine-1-carboxylic acid tert-butyl esterHCID 575254324-[3-(2-Chloro-4-formyl-phenoxy)-propyl]-piperazine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 113161825-Chloro-2-[3-chloro-4-(3-piperazin-1-yl-propoxy)-phenyl]-6-fluoro-1H-benzoimidazole수율 15%

실험 절차

4-{3-[2-Chloro-4-(5-chloro-6-fluoro-1H-benzoimidazol-2-yl)-phenoxy]-propyl}-piperazine-1-carboxylic acid tert-butyl ester. This compound was prepared by the method described in Example 1, using 4-[3-(2-chloro-4-formyl-phenoxy)-propyl]-piperazine-1-carboxylic acid tert-butyl ester (1.0 g, 2.6 mmol, 1.0 equiv), 4-chloro-5-fluoro-benzene-1,2-diamine (421 mg, 2.6 mmol, 1.0 equiv), and Na2S2O5 (648 mg, 3.4 mmol, 1.3 equiv) in General Procedure 3. Purification by Method 2 afforded 256 mg (15%) of the title compound. MS (electrospray): mass calculated for C25H29Cl2FN4O3, 522.16; m/z found, 545.3 [M+Na]+. B. 5-Chloro-2-[3-chloro-4-(3-piperazin-1-yl-propoxy)-phenyl]-6-fluoro-1H-benzoimidazole. To a suspension of 4-{3-[2-chloro-4-(5-chloro-6-fluoro-1H-benzoimidazol-2-yl)-phenoxy]-propyl}-piperazine-1-carboxylic acid tert-butyl ester (52.7 mg, 0.10 mmol) in dichloromethane (1.0 mL) at rt was added TFA (1.0 mL), and the reaction mixture was stirred for 50 min. The mixture was concentrated under reduced pressure, and the solid residue was washed four times with dichloromethane. The title compound was obtained in quantitative yield as the TFA salt. MS (electrospray): mass calculated for C20H21Cl2FN4O, 422.11; m/z found, 423.2 [M+H]+. 1H NMR (400 MHz, CD3OD): 8.17 (d, J=2.3 Hz, 1H), 8.03 (dd, J=8.7, 2.3 Hz, 1H), 7.81 (d, J=6.4 Hz, 1H), 7.59 (d, J=8.7 Hz, 1H), 7.36 (d, J=8.8 Hz, 1H), 4.33 (t, J=5.8 Hz, 2H), 3.50-3.47 (m, 4H), 3.36 (br s, 4H), 3.25 (t, J=7.4 Hz, 2H), 2.33-2.26 (m, 2H).

후처리

  1. customThis compound was prepared by the method
  2. customPurification by Method 2

출처 및 근거

ORD 기록
ord-8b3c155ce6cc44969f0e39ceea16dd41
출처 데이터셋
uspto-grants-2010_05
특허 번호
US07723527B2

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