Triethylamine → N-methoxy-N-methyl-2-(methylthio)pyrimidine-4-carboxamide

HRID 2214773Notes

Reaction equation

HRID 2214773 reaction equation
[CH3:1][S:2][C:3]1[N:8]=[C:7]([C:9]([OH:11])=O)[CH:6]=[CH:5][N:4]=1.Cl.[CH3:13][NH:14][O:15][CH3:16].Cl.CN(C)CCCN=C=NCC.ON1C2N=CC=CC=2N=N1.C(N(CC)CC)C>CN(C=O)C>[CH3:16][O:15][N:14]([CH3:13])[C:9]([C:7]1[CH:6]=[CH:5][N:4]=[C:3]([S:2][CH3:1])[N:8]=1)=[O:11]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 181649HOAtHCID 2957752-(Methylsulfanyl)pyrimidine-4-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 21948429N-methoxy-N-methyl-2-(methylthio)pyrimidine-4-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-(methylthio)pyrimidine-4-carboxylic acid (1-1, prepared according to Kim, C.-H., et al J. Med. Chem. 1986, 29, 1374–1380 and McOmie, W. J. Chem. Soc. 1953, 3129, 2.00 g, 11.8 mmol, 1 equiv), N,O-dimethylhydroxylamine hydrochloride (3.44 g, 35.3 mmol, 3.00 equiv), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (3.38 g, 17.6 mmol, 1.50 equiv), 1-hydroxy-7-azabenzotriazole (2.40 g, 17.6 mmol, 1.50 equiv), and triethylamine (6.55 mL, 47.0 mmol, 4.00 equiv) in DMF (40 mL) was stirred for 20 hours. The reaction mixture was partitioned between a 1:1 mixture of brine and saturated aqueous sodium carbonate solution (100 mL) and ethyl acetate (2×50 mL). The combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography (hexane initially, grading to 40% hexane in ethyl acetate) to give N-methoxy-N-methyl-2-(methylthio)pyrimidine-4-carboxamide (1-2) as a colorless oil. 1H NMR (300 MHz, CDCl3) δ 8.63 (d, 1H, J=4.9 Hz), 7.13 (br s, 1H), 3.74 (br s, 3H), 3.36 (br s, 3H), 2.59 (s, 3H).

Workup

  1. customThe reaction mixture was partitioned between a 1:1 mixture of brine and saturated aqueous sodium carbonate solution (100 mL) and ethyl acetate (2×50 mL)
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. concentrationconcentrated
  4. customThe residue was purified by flash column chromatography (hexane initially

Sources & evidence

ORD record
ord-19de98a35d654a7cb76e63ab84d246dd
Source dataset
uspto-grants-2006_09
Patent number
US07109204B2

Reaction notes

Loading…