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

HRID 1367020Notes

Reaction equation

HRID 1367020 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:66]([F:67])=[CH:65][C:54]2[NH:55][C:56]([CH2:58][CH:59]3[CH2:64][CH2:63][CH2:62][CH2:61][NH:60]3)=[N:57][C:53]=2[CH:52]=1>CN(C=O)C>[F:50][C:51]1[C:66]([F:67])=[CH:65][C:54]2[NH:55][C:56]([CH2:58][CH:59]3[CH2:64][CH2:63][CH2:62][CH2:61][N:60]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])=[N:57][C:53]=2[CH:52]=1

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 17973671HCID 17973671, compoundHCID 223241255-(4-Fluorophenyl)-2-methyl-1,3-thiazole-4-carboxylic acid

Product 1

HCID 17973672(RS)-1-[2-(5,6-Difluoro-1H-benzoimidazol-2-ylmethyl)-piperidin-1-yl]-1-[5-(4-fluoro-phenyl)-2-methyl-thiazol-4-yl]-methanoneYield 97%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 5-(4-fluoro-phenyl)-2-methyl-thiazole-4-carboxylic acid (700 mg, 3.0 mmol), HATU (1.12 g, 3.0 mmol) and N,N-diisopropylethylamine (1.54 ml, 9.0 mmol) in DMF (20 ml) was stirred at room temperature under argon for 2 min. The mixture was then treated with (RS)-5,6-difluoro-2-piperidin-2-ylmethyl-1H-benzoimidazole, D18 (742 mg, 3.0 mmol) and stirring was continued for 16 h. The solvent was removed in vacuo and the residue partitioned between water and ethyl acetate. The organic phase was dried (Na2SO4) and the solvent removed in vacuo. Chromatography (silica gel, 0-5% methanol-ethyl acetate) afforded the title compound as a pale yellow solid (1.35 g, 97%).

Workup

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

Sources & evidence

ORD record
ord-7ead6e7b33db43e3b7c3c17e06f1da78
Source dataset
uspto-grants-2011_02
Patent number
US07893090B2

Reaction notes

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