O-Phenylenediamine → (RS)-1-[2-(1H-benzoimidazol-2-ylmethyl)-piperidin-1-yl]-1-[5-(4-fluoro phenyl)-2-methyl-thiazol-4-yl]-methanone

HRID 598580Notes

Reaction equation

HRID 598580 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([CH3:13])=[N:10][C:9]=2[C:14]([N:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH:17]2[CH2:22][C:23](O)=O)=[O:15])=[CH:4][CH:3]=1.[C:26]1([NH2:33])[C:27]([NH2:32])=[CH:28][CH:29]=[CH:30][CH:31]=1.C([O-])([O-])=O.[K+].[K+]>>[NH:32]1[C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=2[N:33]=[C:23]1[CH2:22][CH:17]1[CH2:18][CH2:19][CH2:20][CH2:21][N:16]1[C:14]([C:9]1[N:10]=[C:11]([CH3:13])[S:12][C:8]=1[C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)=[O:15]

Participants

4

Reactant 3

HCID 7243O-PhenylenediamineHCID 11430Potassium CarbonateHCID 23146320(1-{1-[5-(4-Fluoro-phenyl)-2-methyl-thiazol-4-yl]-methanoyl}-piperidin-2-yl)-acetic acid

Product 1

HCID 17973686(RS)-1-[2-(1H-benzoimidazol-2-ylmethyl)-piperidin-1-yl]-1-[5-(4-fluoro phenyl)-2-methyl-thiazol-4-yl]-methanoneYield 52%

Procedure

(RS)-(1-{1-[5-(4-Fluoro-phenyl)-2-methyl-thiazol-4-yl]-methanoyl}-piperidin-2-yl)-acetic acid, D17 (110 mg, 0.3 mmol) and benzene-1,2-diamine (33 mg, 0.3 mmol) in PPA (2 g) were heated at 140° C. for 3.5 h. The cooled reaction mixture was poured onto a mixture of crushed ice and K2CO3. The basic aqueous solution was extracted with ethyl acetate (3×). The combined organics were washed with brine, dried (MgSO4) and the solvent removed in vacuo. Chromatography (silica gel, ethyl acetate) afforded the title compound as a dark yellow gum (72 mg, 52%).

Workup

  1. customThe cooled reaction mixture
  2. extractionThe basic aqueous solution was extracted with ethyl acetate (3×)
  3. washThe combined organics were washed with brine
  4. dry with materialdried (MgSO4)
  5. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-d731b6c5bd434cd5811acee81bcb7cd3
Source dataset
uspto-grants-2011_03
Patent number
US07897618B2

Reaction notes

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