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Ammonia → 2,6-Dichloropyrimidine-4-carboxamide

HRID 1752388
Notes
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Reaction equation

HRID 1752388 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8](Cl)=[O:9])[CH:5]=[C:4]([Cl:11])[N:3]=1.N.O1CCOCC1.CC[N:21](C(C)C)C(C)C>CCOCC>[Cl:1][C:2]1[N:7]=[C:6]([C:8]([NH2:21])=[O:9])[CH:5]=[C:4]([Cl:11])[N:3]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 222AmmoniaHCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 110311332,6-dichloropyrimidine-4-carbonyl Chloride

Product 1

HCID 2411282,6-Dichloropyrimidine-4-carboxamideYield 41.1%

Reagents, catalysts & solvents 1

HCID 3283
Diethyl Ether
Solvent

Procedure

To a solution of 2,6-dichloropyrimidine-4-carbonyl chloride (26.13 g, 123.6 mmol) in Et2O (500 mL) was added a mixture of 0.5M ammonia in dioxane (250 mL, 125 mmol) and iPr2NEt (22 mL, 126 mmol) dropwise over approximately 50 minutes. After stirring overnight the reaction was concentrated in vacuo to a residue and chromatographed over silica gel with 10-50% EtOAc in hexanes. The product fractions were evaporated in vacuo, and the resulting solid residue triturated with 10 mL 10% EtOAc/hexanes and filtered to give 2,6-dichloropyrimidine-4-carboxamide as an orange crystalline solid (9.743 g, 50.74 mmol, 41% yield). LC/MS: m/z=192.2 [M+H]+, 1H NMR (400 MHz, DMSO-d6): 8.40 (1H, br s), 8.16 (1H, br s), 8.10 (1H, s).

Workup

  1. concentrationwas concentrated in vacuo to a residue
  2. customchromatographed over silica gel with 10-50% EtOAc in hexanes
  3. customThe product fractions were evaporated in vacuo
  4. customthe resulting solid residue triturated with 10 mL 10% EtOAc/hexanes
  5. filtrationfiltered

Sources & evidence

ORD record
ord-ba80fda56709426fb6d2230b453c3d22
Source dataset
uspto-grants-2015_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09163008B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes