Water → N-{{2-chloro-5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1 (2H)-pyrimidinyl]-4-fluoro-phenyl}(thiocarbamoyl)}-beta-alanine, methyl ester

HRID 380791Notes

Reaction equation

HRID 380791 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N:9]2[C:14](=[O:15])[CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[N:11]([CH3:20])[C:10]2=[O:21])=[CH:4][C:3]=1[N:22]=[C:23]=[S:24].Cl.[NH2:26][CH2:27][CH2:28][C:29]([O:31][CH3:32])=[O:30].C(N(CC)CC)C.O>CC(C)=O.C(Cl)Cl.C(Cl)Cl.C(OCC)C>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N:9]2[C:14](=[O:15])[CH:13]=[C:12]([C:16]([F:17])([F:18])[F:19])[N:11]([CH3:20])[C:10]2=[O:21])=[CH:4][C:3]=1[NH:22][C:23]([NH:26][CH2:27][CH2:28][C:29]([O:31][CH3:32])=[O:30])=[S:24]

Participants

8

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 2734767Methyl 3-aminopropanoate hydrochlorideHCID 183659632-Chloro-5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-4-fluoro-phenyl isothiocyanate

Product 1

HCID 20695541N-{{2-chloro-5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1 (2H)-pyrimidinyl]-4-fluoro-phenyl}(thiocarbamoyl)}-beta-alanine, methyl esterYield 74.5%

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 6344DichloromethaneSolventHCID 21881112Ethyl ether methylene chlorideSolvent

Procedure

A solution of 2-chloro-5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-4-fluorophenyl isothiocyanate (6.0 g, 15.8 mmol) and β-alanine, methyl ester, hydrochloride salt (2.65 g, 19.0 mmol) in acetone is cooled to 0° C., treated dropwise with a solution of triethylamine (1.92 g, 19.0 mmol) in methylene chloride, stirred overnight at room temperature, and poured into water. The resultant aqueous mixture is extracted with ethyl acetate. The organic extracts are combined, washed sequentially with 5% hydrochloric acid and brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo to obtain a brown foam. Flash column chromatography of the foam using silica gel and a (9:1) methylene chloride/diethyl ether solution gives the title product as an off-white foam (5.68 g, 74.4% yield, mp 110° C.) which is identified by 1H NMR spectral analysis.

Workup

  1. extractionThe resultant aqueous mixture is extracted with ethyl acetate
  2. washwashed sequentially with 5% hydrochloric acid and brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customto obtain a brown foam

Sources & evidence

ORD record
ord-55e24b86bf8c46668a51af9ceb402762
Source dataset
uspto-grants-2001_10
Patent number
US06303783B1

Reaction notes

Loading…