Hydrochloric Acid → Methyl 2-(4-(4-(6-fluorobenzo[d]thiazol-2-ylamino)phenyl)thiazole-2-carboxamido)-3-methylbutanoate

HRID 1024451Notes

Reaction equation

[CH3:1][CH:2]([CH3:25])[CH:3]([NH:8][C:9]([C:11]1[S:12][CH:13]=[C:14]([C:16]2[CH:21]=[CH:20][C:19]([N+:22]([O-])=O)=[CH:18][CH:17]=2)[N:15]=1)=[O:10])[C:4]([O:6][CH3:7])=[O:5].Cl[C:27]1[S:28][C:29]2[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:30]=2[N:31]=1.Cl>C(O)CCC.O1CCOCC1>[F:36][C:34]1[CH:33]=[CH:32][C:30]2[N:31]=[C:27]([NH:22][C:19]3[CH:20]=[CH:21][C:16]([C:14]4[N:15]=[C:11]([C:9]([NH:8][CH:3]([CH:2]([CH3:25])[CH3:1])[C:4]([O:6][CH3:7])=[O:5])=[O:10])[S:12][CH:13]=4)=[CH:17][CH:18]=3)[S:28][C:29]=2[CH:35]=1

Participants

Conditions

Temperature: 70 °C

Procedure

To methyl-2-(4-(4-aminophenyl)thiazole-2-carboxamido)-3-methylbutanoate (Intermediate 3, 300 mg) in n-butanol (5 ml), 2-chloro-6-fluorobenzo[d]thiazole (202 mg) was added and the reaction mixture was heated at 70° C. and stirred for 10 minutes. 4M HCl in dioxane (0.131 gm) was added and the reaction mixture was stirred for 16 hours at 90° C. Organic solvent was concentrated to obtain a sticky solid, which was purified by column chromatography (silica gel, EtOAc-petroleum ether) to obtain title compound as solid. Yield: 130 mg (29%). 1H NMR (CDCl3; 300 MHz): δ 7.97 (d, 2H), 7.83 (d, 1H), 7.67 (s, 1H), 7.64 (m, 4H), 7.38 (dd, 1H), 7.13 (td, 1H), 4.77 (q, 1H), 3.80 (s, 3H), 2.37 (m, 1H), 0.97 (dd, 6H).

Workup

stirringthe reaction mixture was stirred for 16 hours at 90° C
concentrationOrganic solvent was concentrated
customto obtain a sticky solid, which
customwas purified by column chromatography (silica gel, EtOAc-petroleum ether)

Sources & evidence

ORD record: ord-21887568bbeb448dbb04861acd3f1e6e
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08722901B2

Reaction notes

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