Triethylamine → N-(5-bromo-1,3-thiazol-2-yl)adamantane-1-carboxamide

HRID 1469956

Reaction equation

Br.[NH2:2][C:3]1[S:4][C:5]([Br:8])=[CH:6][N:7]=1.[C:9]12([C:19](Cl)=[O:20])[CH2:18][CH:13]3[CH2:14][CH:15]([CH2:17][CH:11]([CH2:12]3)[CH2:10]1)[CH2:16]2.C(N(CC)CC)C>CN(C)C1C=CN=CC=1.C1COCC1.C(OCC)(=O)C>[Br:8][C:5]1[S:4][C:3]([NH:2][C:19]([C:9]23[CH2:18][CH:13]4[CH2:12][CH:11]([CH2:17][CH:15]([CH2:14]4)[CH2:16]2)[CH2:10]3)=[O:20])=[N:7][CH:6]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 2-amino-5-bromothiazole monohydrobromide (3.00 g, 11.5 mmol), 1-adamantanecarbonyl chloride (2.74 g, 13.8 mmol), 4-dimethylaminopyridine (1.10 g, 0.90 mmol) and triethylamine (3.20 mL, 23.0 mmol) in 100 mL of THF was stirred at 80° C. for 48 hours. The mixture was cooled to ambient temperature, diluted with 100 mL of ethyl acetate and washed with brine. The layers were separated and the aqueous phase was extracted twice with 50 mL of ethyl acetate. The combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated. Purification by column chromatography (SiO2, 20% ethyl acetate: 80% hexane) afforded 2.55 g of the title compound: 1H NMR (400 MHz, DMSO-d6) δ 1.67-1.72 (m, 6H) 1.92 (d, J=2.8 Hz, 6H) 1.97-2.04 (m, 3H) 7.55 (s, 1H) 11.50 (br m, 1H); MS (DCI/NH3) m/z 341 (M)+, 343 (M+2)+.

Workup

temperatureThe mixture was cooled to ambient temperature
washwashed with brine
customThe layers were separated
extractionthe aqueous phase was extracted twice with 50 mL of ethyl acetate
dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
filtrationfiltered
concentrationconcentrated
customPurification by column chromatography (SiO2, 20% ethyl acetate: 80% hexane)

Sources & evidence

ORD record: ord-36454baca6d94fa0851e651c9a5723aa
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09006275B2

Linked notes

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