Diisopropylethylamine → 4-biphenyl-4-ylmethyl-1-[2-(S)-tert-butoxycarbonylamino-3-thiophen-2-yl-propionyl]-piperidine-4-carboxylic acid methyl ester

HRID 2360967Notes

Reaction equation

HRID 2360967 reaction equation
[CH3:1][O:2][C:3]([C:5]1([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:14][CH:13]=2)[CH2:10][CH2:9][NH:8][CH2:7][CH2:6]1)=[O:4].[C:24]([O:28][C:29]([NH:31][C@@H:32]([CH2:36][C:37]1[S:38][CH:39]=[CH:40][CH:41]=1)[C:33](O)=[O:34])=[O:30])([CH3:27])([CH3:26])[CH3:25].C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(OCC)(=O)C>[CH3:1][O:2][C:3]([C:5]1([CH2:11][C:12]2[CH:13]=[CH:14][C:15]([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)=[CH:16][CH:17]=2)[CH2:10][CH2:9][N:8]([C:33](=[O:34])[C@@H:32]([NH:31][C:29]([O:28][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:30])[CH2:36][C:37]2[S:38][CH:39]=[CH:40][CH:41]=2)[CH2:7][CH2:6]1)=[O:4]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 27344843-(Thien-2-yl)-L-alanine, N-BOC protectedHCID 673851234-Biphenyl-4-ylmethyl-piperidine-4-carboxylic acid methyl ester

Product 1

HCID 673851184-biphenyl-4-ylmethyl-1-[2-(S)-tert-butoxycarbonylamino-3-thiophen-2-yl-propionyl]-piperidine-4-carboxylic acid methyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-biphenyl-4-ylmethyl-piperidine-4-carboxylic acid methyl ester (8.73 mmol; 2.7 g) in DMF (20 mL) was added (S)-2-tert-butoxycarbonylamino-3-thiophen-2-yl-propionic acid (9.58 mmol; 2.60 g), N,N-diisopropyl-N-ethylamine (17.46 mmol; 3.1 mL) and HBTU (10.48 mmol; 3.97 g), and the resulting mixture was stirred at room temperature overnight. Ethyl acetate (200 mL) was added and the resulting solution was washed with a 1N hydrochloric acid solution (2×50 mL) and brine (50 mL), and dried over magnesium sulfate. After filtration and evaporation, the residue was purified via flash column chromatography (eluent gradient: 0 to 60% EtOAc in heptane) to yield 4-biphenyl-4-ylmethyl-1-[2-(S)-tert-butoxycarbonylamino-3-thiophen-2-yl-propionyl]-piperidine-4-carboxylic acid methyl ester after evaporation. MS (ESI) m/z 565.36 [M+H]+.

Workup

  1. washthe resulting solution was washed with a 1N hydrochloric acid solution (2×50 mL) and brine (50 mL)
  2. dry with materialdried over magnesium sulfate
  3. filtrationAfter filtration and evaporation
  4. customthe residue was purified via flash column chromatography (eluent gradient: 0 to 60% EtOAc in heptane)

Sources & evidence

ORD record
ord-27476f86452441308da14747f412dffb
Source dataset
uspto-grants-2014_04
Patent number
US08686152B2

Reaction notes

Loading…