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

HRID 1367021Notes

Reaction equation

HRID 1367021 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]([OH:16])=O)=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.[F:50][C:51]1[C:59]2[N:58]=[C:57]([CH2:60][CH:61]3[CH2:66][CH2:65][CH2:64][CH2:63][NH:62]3)[NH:56][C:55]=2[CH:54]=[CH:53][C:52]=1[F:67]>CN(C=O)C>[F:50][C:51]1[C:59]2[N:58]=[C:57]([CH2:60][CH:61]3[CH2:66][CH2:65][CH2:64][CH2:63][N:62]3[C:14]([C:9]3[N:10]=[C:11]([CH3:13])[S:12][C:8]=3[C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)=[O:16])[NH:56][C:55]=2[CH:54]=[CH:53][C:52]=1[F:67]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 17973676(RS)-4,5-Difluoro-2-piperidin-2-ylmethyl-1H-benzoimidazoleHCID 223241255-(4-Fluorophenyl)-2-methyl-1,3-thiazole-4-carboxylic acid

Product 1

HCID 17973673(RS)-1-[2-(4,5-Difluoro-1H-benzoimidazol-2-ylmethyl)-piperidin-1-yl]-1-[5-(4-fluoro-phenyl)-2-methyl-thiazol-4-yl]-methanoneYield 85%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 5-(4-fluoro-phenyl)-2-methyl-thiazole-4-carboxylic acid (1.00 g, 4.2 mmol), HATU (1.60 g, 4.2 mmol) and N,N-diisopropylethylamine (2.00 ml, 11.6 mmol) in DMF (20 ml) was stirred at room temperature under argon for 2 min. The mixture was then treated with (RS)-4,5-difluoro-2-piperidin-2-ylmethyl-1H-benzoimidazole, D21 (1.06 g, 4.2 mmol) and stirring was continued for 16 h. The solvent was removed in vacuo and the residue was washed with water then was triturated with ethyl acetate to afford the title compound as an off-white solid (1.68 g, 85%).

Workup

  1. customThe solvent was removed in vacuo
  2. washthe residue was washed with water
  3. customthen was triturated with ethyl acetate

Sources & evidence

ORD record
ord-3447a27ee38f436ebfdf371234dc95c8
Source dataset
uspto-grants-2011_02
Patent number
US07893090B2

Reaction notes

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