Diisopropylethylamine → 2-[2-(4-Bromo-phenyl)-2-oxo-ethylcarbamoyl]-4-cyano-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1185955Notes

Reaction equation

HRID 1185955 reaction equation
Cl.[NH2:2][CH2:3][C:4]([C:6]1[CH:11]=[CH:10][C:9]([Br:12])=[CH:8][CH:7]=1)=[O:5].[C:13]([O:17][C:18]([N:20]1[CH2:24][CH:23]([C:25]#[N:26])[CH2:22][CH:21]1[C:27](O)=[O:28])=[O:19])([CH3:16])([CH3:15])[CH3:14].C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(OCC)(=O)C>[C:13]([O:17][C:18]([N:20]1[CH2:24][CH:23]([C:25]#[N:26])[CH2:22][CH:21]1[C:27](=[O:28])[NH:2][CH2:3][C:4]([C:6]1[CH:11]=[CH:10][C:9]([Br:12])=[CH:8][CH:7]=1)=[O:5])=[O:19])([CH3:16])([CH3:15])[CH3:14]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 27982162-Amino-1-(4-bromophenyl)ethan-1-one hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 14842640(2S,4S)-1-(tert-Butoxycarbonyl)-4-cyano-2-pyrrolidinecarboxylic acid

Product 1

HCID 666213862-[2-(4-Bromo-phenyl)-2-oxo-ethylcarbamoyl]-4-cyano-pyrrolidine-1-carboxylic acid tert-butyl esterYield 91%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

2-Amino-1-(4-bromo-phenyl)-ethanone HCl salt (664 mg, 2.65 mmol) was dissolved in DMF (10 mL) and to this solution was added 4-Cyano-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester crude from the previous step, diisopropyl ethylamine (0.93 mL, 5.3 mmol), followed by HATU (1 g, 2.65 mmol). Reaction mixture was stirred at 0° C. for 30 minutes. The reaction mixture was dissolved in ethyl acetate and washed with dilute sodium bicarbonate solution. The organic layer was dried (MgSO4), concentrated and purified by flash column chromatography (silica gel, 20 to 80% ethyl acetate/hexane) to give 2-[2-(4-Bromo-phenyl)-2-oxo-ethylcarbamoyl]-4-cyano-pyrrolidine-1-carboxylic acid tert-butyl ester (1.05 g, yield 91%). LCMS-ESI−: calc'd for C19H22BrN3O4: 435.08. Found: 458.0 (M+Na+).

Workup

  1. customReaction mixture
  2. washwashed with dilute sodium bicarbonate solution
  3. dry with materialThe organic layer was dried (MgSO4)
  4. concentrationconcentrated
  5. custompurified by flash column chromatography (silica gel, 20 to 80% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-5dd16c5eeb7846aabfd73b35e5b24149
Source dataset
uspto-grants-2014_03
Patent number
US08669234B2

Reaction notes

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