4-Chloro-2-(methylthio)pyrimidine-5-carboxylic acid ethyl ester → HCID 849409, compound

HRID 2251084Notes

Reaction equation

[CH2:1]([O:3][C:4]([C:6]1[C:7](Cl)=[N:8][C:9]([S:12][CH3:13])=[N:10][CH:11]=1)=[O:5])[CH3:2].[NH2:15][C:16]1[N:20]([CH3:21])[N:19]=[C:18]([CH3:22])[CH:17]=1>C(O)C>[CH2:1]([O:3][C:4]([C:6]1[C:7]([NH:15][C:16]2[N:20]([CH3:21])[N:19]=[C:18]([CH3:22])[CH:17]=2)=[N:8][C:9]([S:12][CH3:13])=[N:10][CH:11]=1)=[O:5])[CH3:2]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 4-chloro-2-methylsulfanyl-pyrimidine-5-carboxylic acid ethyl ester (4.6 g, 19.6 mmol) in ethanol (90 mL) is added 5-amino-1,3-dimethylpyrazole (4.4 g, 39.2 mmol). The mixture is heated for 22 hours at 80° C. The reaction is cooled to room temp and concentrated in vacuo. The solid which remains is dissolved in CHCl3 and washed with aqueous saturated NaHCO3 solution. The organic phase is dried (MgSO4), filtered and concentrated in vacuo and the resulting residue is purified over silica (50% EtOAc//hexanes, followed by 100% EtOAc) to afford 4.8 g of the desired product: 1H NMR (300 MHz, CDCl3) δ10.29 (s, NH), 8.82 (s, 1H), 6.30 (s, 1H), 4.43 (q, J=7.2 Hz, 2H), 3.77 (s, 3H), 2.53 (s, 3H), 2.30 (s, 3H), 1.45 (t, J=7.2 Hz, 3H); ESI+ MS: m/z (rel intensity) 308.0 (100, M++H).

Workup

temperatureThe reaction is cooled to room temp
concentrationconcentrated in vacuo
dissolutionThe solid which remains is dissolved in CHCl3
washwashed with aqueous saturated NaHCO3 solution
dry with materialThe organic phase is dried (MgSO4)
filtrationfiltered
concentrationconcentrated in vacuo
customthe resulting residue is purified over silica (50% EtOAc//hexanes, followed by 100% EtOAc)

Sources & evidence

ORD record: ord-448fe476ba9c4e8db6c2440cfb53c2bf
Source dataset: uspto-grants-2008_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07319102B1

Reaction notes

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