4-Fluoro-3-methylbenzene-1,2-diamine → HCID 178429740, 화합물

HRID 646974노트

반응식

HRID 646974 반응식
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([O:8][CH2:9][CH2:10][CH2:11][O:12][C:13]2[CH:14]=[C:15]([CH:18]=[CH:19][CH:20]=2)[CH:16]=O)[CH2:4][CH2:3]1.[F:21][C:22]1[C:23]([CH3:30])=[C:24]([NH2:29])[C:25]([NH2:28])=[CH:26][CH:27]=1>CN(C=O)C>[F:21][C:22]1[CH:27]=[CH:26][C:25]2[N:28]=[C:16]([C:15]3[CH:18]=[CH:19][CH:20]=[C:13]([O:12][CH2:11][CH2:10][CH2:9][O:8][CH:5]4[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]4)[CH:14]=3)[NH:29][C:24]=2[C:23]=1[CH3:30]

참가 물질

4

반응물 2

HCID 220555474-Fluoro-3-methylbenzene-1,2-diamineHCID 574809313-[3-(1-Methyl-piperidin-4-yloxy)-propoxy]-benzaldehyde

생성물 1

HCID 178429740HCID 178429740, 화합물수율 37.8%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

6-Fluoro-7-methyl-2-{3-[3-(1-methyl-piperidin-4-yloxy)-propoxy]-phenyl}-1H-benzoimidazole. To a stirred solution of 3-[3-(1-methyl-piperidin-4-yloxy)-propoxy]-benzonitrile (0187 g, 0.68 mmol, 1.0 equiv) in toluene (5.0 mL) at 0° C. was added 1.5 M diisobutylaluminum hydride in toluene (1.02 mL, 1.02 mmol, 1.5 equiv). After 3 h, methanol (9 mL) and 1 M H2SO4 (10 mL) were added. The mixture was stirred for 30 min, then 1.0 M NaOH (10 mL) was added, followed by satd. aq. sodium potassium tartrate (40 mL) and dichloromethane (100 mL). After stirring for 30 min, the mixture was extracted three times with chloroform (50 mL) and the combined extracts were washed with brine, dried (Na2SO4), filtered, and concentrated. The residue was partially purified by Method 2 to afford 106 mg of a mixture of 3-[3-(1-methyl-piperidin-4-yloxy)-propoxy]-benzaldehyde and several other unidentified products. A solution of the crude 3-[3-(1-methyl-piperidin-4-yloxy)-propoxy]-benzaldehyde (53 mg), 4-fluoro-3-methyl-benzene-1,2-diamine (27 mg), and Na2S2O5 in DMF was stirred at 90° C. for 18 h. The reaction mixture was loaded directly on silica gel and purified according to Method 2, which afforded 28.7 mg of the title compound. MS (electrospray): mass calculated for C23H28FN3O2, 397.22. m/z found, 398.4 [M+H]+. 1H NMR (400 MHz, CD3OD): 7.64-7.53 (m, 2H), 7.38-7.25 (m, 2H), 7.00-6.85 (m, 2H), 4.06 (t, J=6.1 Hz, 2H), 3.60-3.52 (m, 2H), 3.33-3.19 (br s, 1H), 2.58 (br s, 2H), 2.42 (s, 3H), 2.17-2.03 (m, 5H), 2.01-1.90 (m, 2H), 1.86-1.72 (m, 2H), 1.60-1.42 (m, 2H).

후처리

  1. custompurified

출처 및 근거

ORD 기록
ord-44ba7e4b3d124daa9ec267c3830f7a35
출처 데이터셋
uspto-grants-2010_04
특허 번호
US07705149B2

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