4-Fluoro-3-methylbenzene-1,2-diamine → HCID 178429740、化合物

HRID 646974ノート

反応式

HRID 646974 の反応式
[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]

参加物

4

反応物 2

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

生成物 1

HCID 178429740HCID 178429740、化合物収率 37.8%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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).

後処理

  1. custompurified

出典と根拠

ORDレコード
ord-44ba7e4b3d124daa9ec267c3830f7a35
出典データセット
uspto-grants-2010_04
特許番号
US07705149B2

反応ノート

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