Diisopropylethylamine → 6-(4-Chloro-phenyl)-5-(2-methoxy-ethoxy)-pyrazine-2-carboxylic acid (1-hydroxymethyl-cyclopropyl)-amide

HRID 1865891Notes

Reaction equation

HRID 1865891 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]([C:14]([OH:16])=O)[CH:11]=[N:10][C:9]=2[O:17][CH2:18][CH2:19][O:20][CH3:21])=[CH:4][CH:3]=1.ClC(N(C)C)=C(C)C.Cl.[NH2:31][C:32]1([CH2:35][OH:36])[CH2:34][CH2:33]1.C(N(C(C)C)C(C)C)C>ClCCl>[OH:36][CH2:35][C:32]1([NH:31][C:14]([C:12]2[CH:11]=[N:10][C:9]([O:17][CH2:18][CH2:19][O:20][CH3:21])=[C:8]([C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)[N:13]=2)=[O:16])[CH2:34][CH2:33]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 14146222(1-Aminocyclopropyl)methanol hydrochlorideHCID 687990096-(4-Chloro-phenyl)-5-(2-methoxy-ethoxy)-pyrazine-2-carboxylic acid

Product 1

HCID 688414796-(4-Chloro-phenyl)-5-(2-methoxy-ethoxy)-pyrazine-2-carboxylic acid (1-hydroxymethyl-cyclopropyl)-amideYield 57.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 0.05 g (0.00016 mol) of 6-(4-chloro-phenyl)-5-(2-methoxy-ethoxy)-pyrazine-2-carboxylic acid in 2.0 ml dichloromethane was added 0.024 g 1-chloro-N,N,2-trimethyl-1-propenylamine and the mixture was stirred at room temperature for 30 min. To the resulting slightly brown solution was added 0.040 g of (1-amino-cyclopropyl)-methanol hydrochloride and dropwise 0.1 ml N-ethyldiisopropyl-amine. The mixture was stirred at ambient temperature for 30 min. The resulting mixture was partitioned between 10% aqueous citric acid and ethyl acetate. The phases were separated and the organic phase was dried over magnesium sulfate and evaporated. The residue was purified by chromatography on silica gel using a gradient of heptane to ethyl acetate to yield 0.035 g (55% yield) of the title compound as off white solid. MS (ISP) (M+H+)=378.3.

Workup

  1. stirringThe mixture was stirred at ambient temperature for 30 min
  2. customThe resulting mixture was partitioned between 10% aqueous citric acid and ethyl acetate
  3. customThe phases were separated
  4. dry with materialthe organic phase was dried over magnesium sulfate
  5. customevaporated
  6. customThe residue was purified by chromatography on silica gel using a gradient of heptane to ethyl acetate

Sources & evidence

ORD record
ord-acf34f4754b84ff58a0652fe8015bbd0
Source dataset
uspto-grants-2009_12
Patent number
US07629346B2

Reaction notes

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