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

HRID 1445159Notes

Reaction equation

HRID 1445159 reaction equation
[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]

Participants

4

Reactant 2

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

Product 1

HCID 178429740HCID 178429740, compoundYield 37.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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.

Workup

  1. custompurified

Sources & evidence

ORD record
ord-72a0f383df714520943243a23f9081e8
Source dataset
uspto-grants-2010_02
Patent number
US07662966B2

Reaction notes

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