Triethylamine hydrochloride → HCID 178507563, compound

Temperature

100 °C

To a mixture of 2-amino-6-chlorobenzonitrile (500 mg, 3.3 mmol), sodium azide (4.3 mmol, 1.3 eq.), and triethylamine hydrochloride (4.3 mmol, 1.3 eq.) in a sealed tube, 8 mL of toluene was added. The tube was tightly capped and the reaction was stirred and heated to 100° C. overnight. The mixture was cooled to room temperature, diluted with another 10 mL of toluene, transferred to a separatory funnel and washed with water (3×20 mL). The aqueous extractions were combined and acidified to a pH of 4 with concentrated HCl. The solid was collected by filtration, washed with acetonitrile, and dried under vacuum to afford 137 mg of 3-chloro-2-(1H-tetrazol-5-yl)aniline. MS (EI) for C7H6ClN5: 196 (M+H). Step 2: N-[3-Chloro-2-(1H-tetrazol-5-yl)phenyl]thiophene-2-carboxamide: To a solution of the tetrazole intermediate 3-chloro-2-(1H-tetrazol-5-yl)aniline (137 mg, 0.7 mmol) in 3 mL of DCM, DIPEA (1.4 mmol, 2.0 eq.) was added followed by thiophene-2-carbonyl chloride (1.0 mmol, 1.5 eq.). The reaction was stirred at room temperature overnight. The organic solution of the crude reaction mixture was extracted twice with aqueous HCl (0.1 M), twice with aqueous sodium hydroxide (0.1 M), and once with a saturated aqueous solution of sodium chloride. The basic aqueous extractions and final brine extraction were combined and acidified to a pH of 4 with concentrated HCl. The resulting solid was collected by filtration. This was then washed with acetonitrile, and dried under vacuum to afford 80 mg of desired N-[3-chloro-2-(1H-tetrazol-5-yl)phenyl]thiophene-2-carboxamide. 1H-NMR (400 MHz, d6-DMSO): 10.25 (s, 1H), 7.83 (dd, 1H), 7.73 (dd, 1H), 7.68-7.64 (m, 2H), 7.62-7.59 (m, 1H), 7.17 (t, 1H). MS (EI) for C12H8ClN5OS: 306 (M+H).

1. customThe tube was tightly capped
2. temperatureThe mixture was cooled to room temperature
3. customtransferred to a separatory funnel
4. washwashed with water (3×20 mL)
5. extractionThe aqueous extractions
6. filtrationThe solid was collected by filtration
7. washwashed with acetonitrile
8. customdried under vacuum

ORD record

ord-02f9096bd81c4ad3ad74f58c65cc5e72

Source dataset

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08053454B2