Hydrochloric Acid → 4-(4-chlorobenzyl)-6-methoxy-2-(3-(thiazol-2-ylamino)phenyl)-1,2,4-triazine-3,5(2H,4H)-dione

HRID 1799484Notes

Reaction equation

[NH2:1][C:2]1[CH:3]=[C:4]([N:8]2[C:13](=[O:14])[N:12]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[C:11](=[O:23])[C:10]([O:24][CH3:25])=[N:9]2)[CH:5]=[CH:6][CH:7]=1.Br[C:27]1[S:28][CH:29]=[CH:30][N:31]=1.Cl>C(O)C>[Cl:22][C:19]1[CH:20]=[CH:21][C:16]([CH2:15][N:12]2[C:11](=[O:23])[C:10]([O:24][CH3:25])=[N:9][N:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([NH:1][C:27]4[S:28][CH:29]=[CH:30][N:31]=4)[CH:3]=3)[C:13]2=[O:14])=[CH:17][CH:18]=1

Participants

Conditions

Temperature: 100 °C

Procedure

According to Scheme 9 Step 2: To a Solution of 2-(3-Aminophenyl)-4-(4-chlorobenzyl)-6-methoxy-1,2,4-triazine-3,5(2H,4H)-dione (125 mg, 0.34 mmol) in ethanol (10 ml) was added bromothiazole (124 μL, 1.4 mmol) and 5 mL of concentrated hydrochloric acid. The reaction mixture was heated to 100° C. for 48 hours. The reaction mixture was quenched and neutralised with sat NaHCO3 and extracted in ethyl acetate (×3). The organic layers were combined and successively washed with water, brine, dried over MgSO4, filtered and concentrated. The crude oily solid was purified by flash chromatography, 10 g prepacked column, cyclohexane/ethyl acetate 70/30 to afford 4-(4-chlorobenzyl)-6-methoxy-2-(3-(thiazol-2-ylamino)phenyl)-1,2,4-triazine-3,5(2H,4H)-dione 4.144 (10 mg (Yield=6.5%) as a white solid.

Workup

customThe reaction mixture was quenched
extractionextracted in ethyl acetate (×3)
washsuccessively washed with water, brine
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated
customThe crude oily solid was purified by flash chromatography, 10 g

Sources & evidence

ORD record: ord-3ba5189860a848c7931eddb95421bf1c
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08344138B2

Reaction notes

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