Trifluoroacetic acid → 1-[4-methoxy-7-(3-methyl-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl]-2-[4-[(1-methylimidazol-4-yl)-phenyl-methylene]-1-piperidyl]ethane-1,2-dione

HRID 1394447Notes

Reaction equation

HRID 1394447 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH2:12][C:11](=[C:14]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:15]2[N:16]=[CH:17][N:18]([CH3:20])[CH:19]=2)[CH2:10][CH2:9]1)=[O:7])(C)(C)C.C(O)(C(F)(F)F)=O.Cl.[CH3:35][O:36][C:37]1[CH:45]=[N:44][C:43]([N:46]2[CH:50]=[N:49][C:48]([CH3:51])=[N:47]2)=[C:42]2[C:38]=1[C:39]([C:52](=[O:56])C(O)=O)=[CH:40][NH:41]2.C(N(CC)CC)(C)C.C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1>C(Cl)Cl>[C:21]1([C:14](=[C:11]2[CH2:12][CH2:13][N:8]([C:6](=[O:7])[C:52]([C:39]3[C:38]4[C:42](=[C:43]([N:46]5[CH:50]=[N:49][C:48]([CH3:51])=[N:47]5)[N:44]=[CH:45][C:37]=4[O:36][CH3:35])[NH:41][CH:40]=3)=[O:56])[CH2:9][CH2:10]2)[C:15]2[N:16]=[CH:17][N:18]([CH3:20])[CH:19]=2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 521913N,N-Diethyl-2-propanamineHCID 670462534-Methoxy-7-(3-methyl-1,2,4-triazol-1-yl)-6-azaindol-3-yl-oxoacetic acid hydrochloride saltHCID 670463994-[1-Phenyl-1-(1-methylimidazol-4-yl)methylene]piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 52799431-[4-methoxy-7-(3-methyl-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl]-2-[4-[(1-methylimidazol-4-yl)-phenyl-methylene]-1-piperidyl]ethane-1,2-dioneYield 51.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To solution of 4-[1-phenyl-1-(1-methylimidazol-4-yl)methylene]piperidine-1-carboxylic acid tert-butyl ester(0.0477 g, 0.0775 mmol) in CH2Cl2 (3 mL) was added TFA (0.3 mL) and the solution was allowed to stir at rt for 30 min. The solvent was then removed in vacuo and the material was dissolved in CHCl3. To this solution was added 4-methoxy-7-(3-methyl-1,2,4-triazol-1-yl)-6-azaindol-3-yl-oxoacetic acid hydrochloride salt (0.0258 g, 0.0764 mmol) and iPrNEt2 (0.024 mL, 1.38 mmol), followed by BOP—Cl (0.0271 g, 0.106 mmol). The mixture was allowed to stir at rt for 2 h and then the solvent was removed in vacuo and the residue was partitioned with H2O-EtOAc. The aqueous phase was re-extracted with EtOAc (×2) and the combined organic layers were washed (H2O, brine),dried (Na2SO4) and evaporated. The resulting residue was purified by preparative HPLC (NH4OAc) to give the title compound (0.0210 g, 50%) as a colorless solid:

Workup

  1. customThe solvent was then removed in vacuo
  2. dissolutionthe material was dissolved in CHCl3
  3. stirringto stir at rt for 2 h
  4. customthe solvent was removed in vacuo
  5. customthe residue was partitioned with H2O-EtOAc
  6. extractionThe aqueous phase was re-extracted with EtOAc (×2)
  7. washthe combined organic layers were washed (H2O, brine),dried (Na2SO4)
  8. customevaporated
  9. customThe resulting residue was purified by preparative HPLC (NH4OAc)

Sources & evidence

ORD record
ord-caa2b39f69e648b1afe234ea9b46b9ee
Source dataset
uspto-grants-2008_03
Patent number
US07348337B2

Reaction notes

Loading…