1-Hydroxybenzotriazole → (RS)-1-[2-(5,6-Difluoro-1H-benzoimidazol-2-ylmethyl)-piperidin-1-yl]-1-[5-(4-fluoro-phenyl)-2-hydroxymethyl-thiazol-4-yl]-methanone

HRID 2077322Notes

Reaction equation

HRID 2077322 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([CH2:13][OH:14])=[N:10][C:9]=2[C:15]([OH:17])=O)=[CH:4][CH:3]=1.CCN=C=NCCCN(C)C.Cl.ON1C2C=CC=CC=2N=N1.[F:40][C:41]1[C:56]([F:57])=[CH:55][C:44]2[NH:45][C:46]([CH2:48][CH:49]3[CH2:54][CH2:53][CH2:52][CH2:51][NH:50]3)=[N:47][C:43]=2[CH:42]=1>CN(C=O)C>[F:40][C:41]1[C:56]([F:57])=[CH:55][C:44]2[NH:45][C:46]([CH2:48][CH:49]3[CH2:54][CH2:53][CH2:52][CH2:51][N:50]3[C:15]([C:9]3[N:10]=[C:11]([CH2:13][OH:14])[S:12][C:8]=3[C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)=[O:17])=[N:47][C:43]=2[CH:42]=1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 17973671HCID 17973671, compoundHCID 234501385-(4-Fluoro-phenyl)-2-hydroxymethyl-thiazole-4-carboxylic acid

Product 1

HCID 17973696(RS)-1-[2-(5,6-Difluoro-1H-benzoimidazol-2-ylmethyl)-piperidin-1-yl]-1-[5-(4-fluoro-phenyl)-2-hydroxymethyl-thiazol-4-yl]-methanoneYield 36%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A stirring solution of 5-(4-fluoro-phenyl)-2-hydroxymethyl-thiazole-4-carboxylic acid (632 mg, 2.0 mmol, 80% pure), EDC.HCl (311 mg, 2.0 mmol) and 1-hydroxybenzotriazole (270 mg, 2.0 mmol) in DMF (20 ml) was treated with (RS)-5,6-difluoro-2-piperidin-2-ylmethyl-1H-benzoimidazole, D18 (500 mg, 2.0 mmol). The reaction mixture was stirred at room temperature, under argon for 16 h. The DMF was removed in vacuo and the residue was partitioned between ethyl acetate and water. The organic phase was dried (Na2SO4) and the solvent removed in vacuo. Chromatography (silica gel, 0-10% methanol-ethyl acetate) afforded the title compound as a pale yellow solid (350 mg, 36%).

Workup

  1. customThe DMF was removed in vacuo
  2. customthe residue was partitioned between ethyl acetate and water
  3. dry with materialThe organic phase was dried (Na2SO4)
  4. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-ec3864e4c7bd403c8f102d06e20b242f
Source dataset
uspto-grants-2011_04
Patent number
US07928124B2

Reaction notes

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