Trifluoroacetic acid → Piperidine, 1-[2-[4-methoxy-7-(3-methyl-1H-pyrazol-5-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl]-1,2-dioxoethyl]-4-[(5-methyl-1,3,4-oxadiazol-2-yl)phenylmethylene]-

HRID 606780Notes

Reaction equation

HRID 606780 reaction equation
C([O:5][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[O:16][C:17]([CH3:20])=[N:18][N:19]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.[C:27](O)(C(F)(F)F)=O.Cl.[CH3:35][O:36][C:37]1[CH:45]=[N:44][C:43]([C:46]2[CH:47]=[CH:48][N:49](C)[N:50]=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[CH2:10][CH2:9][N:8]([C:6](=[O:5])[C:52]([C:39]3[C:38]4[C:42](=[C:43]([C:46]5[CH:47]=[C:48]([CH3:27])[NH:49][N:50]=5)[N:44]=[CH:45][C:37]=4[O:36][CH3:35])[NH:41][CH:40]=3)=[O:56])[CH2:13][CH2:12]2)[C:15]2[O:16][C:17]([CH3:20])=[N:18][N:19]=2)[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 521913N,N-Diethyl-2-propanamineHCID 670464714-[1-Phenyl-1-(5-methyl-1,3,4-oxadiazol-2-yl)methylene]-piperidine-1-carboxylic acid tert-butyl esterHCID 670465744-Methoxy-7-(2-methylpyrazol-5-yl)-6-azaindol-3-yl-oxoacetic acid hydrochloride salt

Product 1

HCID 5279947Piperidine, 1-[2-[4-methoxy-7-(3-methyl-1H-pyrazol-5-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl]-1,2-dioxoethyl]-4-[(5-methyl-1,3,4-oxadiazol-2-yl)phenylmethylene]-Yield 6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-[1-phenyl-1-(5-methyl-1,3,4-oxadiazol-2-yl)methylene]piperidine-1-carboxylic acid tert-butyl ester (0.0430 g, 0.167 mmol) in CH2Cl2 (2 mL) was added TFA (0.3 mL) and the reaction mixture was stirred for 30 min. The solvent was then removed in vacuo and the residual material was dissolved in CHCl3 (2 mL). To this solution was added 4-methoxy-7-(2-methylpyrazol-5-yl)-6-azaindol-3-yl-oxoacetic acid hydrochloride salt (0.050 g, 0.167 mmol) and iPrNEt2 (0.145 mL, 0.833 mmol), followed by BOP-Cl (0.0590 g, 0.233 mmol). The mixture was allowed to stir at rt for 2 h and then the solvent was removed in vacuo. The residue was diluted with H2O and extracted with EtOAc (×3). The combined organic layers were washed (H2O, brine), dried (Na2SO4) and concentrated and the residue was purified by preparative HPLC (TFA) to give the title compound (0.0053 g, 6%) as a colorless solid:

Workup

  1. customThe solvent was then removed in vacuo
  2. dissolutionthe residual material was dissolved in CHCl3 (2 mL)
  3. stirringto stir at rt for 2 h
  4. customthe solvent was removed in vacuo
  5. additionThe residue was diluted with H2O
  6. extractionextracted with EtOAc (×3)
  7. washThe combined organic layers were washed (H2O, brine)
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated
  10. customthe residue was purified by preparative HPLC (TFA)

Sources & evidence

ORD record
ord-5523dad65d6147ec9dbbdc999e9e3441
Source dataset
uspto-grants-2011_03
Patent number
US07915283B2

Reaction notes

Loading…