Triethylamine → 2-chloro-N-methoxy-N-methylpyrimidine-4-carboxamide

HRID 410430Notes

Reaction equation

HRID 410430 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8]([OH:10])=O)[CH:5]=[CH:4][N:3]=1.Cl.[CH3:12][O:13][NH:14][CH3:15].C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1>ClCCl.CCOC(C)=O>[Cl:1][C:2]1[N:7]=[C:6]([C:8]([N:14]([O:13][CH3:12])[CH3:15])=[O:10])[CH:5]=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 2724699PyBOPHCID 221357512-Chloropyrimidine-4-carboxylic acid

Product 1

HCID 772313502-chloro-N-methoxy-N-methylpyrimidine-4-carboxamideYield 66%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-chloropyrimidine-4-carboxylic acid (3.95 g, 24.9 mmol) and N-methoxymethanamine hydrogen chloride salt (2.43 g, 24.9 mmol) in dichloromethane (15 mL) were added triethylamine (6.95 mL, 50 mmol) and (benzotriazol-1-yloxy)tripyrrolidino-phosphonium hexafluorophosphate (13 g, 24.91 mmol) and stirred for 4 hr. The solution was diluted with EtOAc, washed with brine, dried with MgSO4, filtered, and concentrated to dryness. Purification on silica gel by flash chromatography (0-100% EtOAc/hexanes) afforded 2-chloro-N-methoxy-N-methylpyrimidine-4-carboxamide (3.30 g, 16.37 mmol, 66% yield). MS ESI: [M+H]+ m/z 202.0. 1H NMR (500 MHz, CDCl3) δ 8.75 (d, J=4.6, 1H), 7.48 (d, J=4.6, 1H), 3.77 (s, 3H), 3.35 (s, 3H).

Workup

  1. washwashed with brine
  2. dry with materialdried with MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated to dryness
  5. customPurification on silica gel by flash chromatography (0-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-47084f65e49a46839ea2c8ad76730cb9
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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