Diisopropylethylamine → 5-Bromo-6-chloro-N-((R)-1-hydroxymethyl-3-methyl-butyl)-nicotinamide

HRID 1159225Notes

Reaction equation

HRID 1159225 reaction equation
[Br:1][C:2]1[C:3]([Cl:11])=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)C(C)C)(C)C.[NH2:43][C@@H:44]([CH2:49][OH:50])[CH2:45][CH:46]([CH3:48])[CH3:47]>CC(N(C)C)=O>[Br:1][C:2]1[C:3]([Cl:11])=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([NH:43][C@@H:44]([CH2:49][OH:50])[CH2:45][CH:46]([CH3:48])[CH3:47])=[O:9]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2854335-Bromo-6-chloropyridine-3-carboxylic acidHCID 2724002D(-)-LeucinolHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate

Product 1

HCID 866195685-Bromo-6-chloro-N-((R)-1-hydroxymethyl-3-methyl-butyl)-nicotinamideYield 91.6%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

5-Bromo-6-chloro-nicotinic acid (2.0 g, 8.46 mmol) was dissolved in DMA (20 mL). To the solution was added TBTU (3.1 g, 9.3 mmol), N,N-diisopropylethyl amine (7.4 mL, 42 mmol) and (D)-leucinol (1.1 g, 9.3 mmol). The reaction mixture was stirred for 16 h at room temperature. The solvent was evaporated in vacuo and the residue was purified by column chromatography on silica (cyclohexane/ethyl acetate gradient) to yield 2.6 g of the title compound as a yellow oil, MS (ISP) 337.1 (M+H)+.

Workup

  1. customThe solvent was evaporated in vacuo
  2. customthe residue was purified by column chromatography on silica (cyclohexane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-e9dedc8e15ba499881ca1fcbcf83bfbd
Source dataset
uspto-grants-2010_10
Patent number
US07812028B2

Reaction notes

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