Triethylamine hydrochloride → HCID 178424089, compound

HRID 555915Notes

Reaction equation

HRID 555915 reaction equation
[NH2:1][C:2]1[CH:9]=[C:8]([CH3:10])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[N-:11]=[N+:12]=[N-:13].[Na+].Cl.C(N(CC)CC)C>C1(C)C=CC=CC=1>[CH3:10][C:8]1[CH:7]=[CH:6][C:3]([C:4]2[NH:13][N:12]=[N:11][N:5]=2)=[C:2]([CH:9]=1)[NH2:1]

Participants

5

Reactant 3

HCID 11130Triethylamine hydrochlorideHCID 33557Sodium AzideHCID 28012762-Amino-4-methylbenzonitrile

Product 1

HCID 178424089HCID 178424089, compoundYield 42.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
100 °C

Procedure

To a mixture of 2-amino-4-methylbenzonitrile (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 3×20 mL with water. The aqueous layer was collected 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 244 mg of 5-methyl-2-(1H-tetrazol-5-yl)aniline. MS (EI) for C8H9N5: 176 (M+H). Step 2: N-[5-Methyl-2-(1H-tetrazol-5-yl)phenyl]thiophene-2-carboxamide: To a solution of 5-methyl-2-(1H-tetrazol-5-yl)aniline (240 mg, 1.4 mmol) in 6 mL of DCM was added DIPEA (7.5 mmol, 5.5 eq.) followed by thiophene-2-carbonyl chloride (6.8 mmol, 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 crude material was further purified by redissolving the material into minimum volume of aqueous NaOH (0.1 M), and then reacidified with concentrated HCl. The solid was collected by filtration, washed with EtOAc, and dried under vacuum to afford 26.8 mg of the desired product. 1H-NMR (400 MHz, d6-DMSO): δ 11.60 (s, 1H), 8.35 (s, 1H), 7.98-7.94 (m, 2H), 7.90 (d, 1H), 7.33 (t, 1H), 7.20 (d, 1H), 2.42 (s, 3H). MS (EI) for C13H11N5OS: 286 (M+H).

Workup

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

Sources & evidence

ORD record
ord-7f4edc32ac8a4358a73c3213198005bf
Source dataset
uspto-grants-2011_11
Patent number
US08053454B2

Reaction notes

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