Pyridine → HCID 178470182, compound

HRID 2088423Notes

Reaction equation

HRID 2088423 reaction equation
[C:1](=S)([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Br)C1C=CC=CC=1.Br.C(SCC1C=CC=CC=1)(=N)C1C=CC=CC=1.N1C=CC=CC=1.[NH2:41][CH:42]([C:48]#[N:49])[C:43]([O:45][CH2:46][CH3:47])=[O:44]>C1COCC1.C(Cl)(Cl)Cl>[NH2:49][C:48]1[NH:8][C:1]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[N:41][C:42]=1[C:43]([O:45][CH2:46][CH3:47])=[O:44]

Participants

8

Reactant 5

HCID 1049PyridineHCID 7498Benzyl BromideHCID 288716Ethyl 2-amino-2-cyanoacetateHCID 683563ThiobenzamideHCID 12624654S-benzylthiobenzimidate hydrobromide

Product 1

HCID 178470182HCID 178470182, compoundYield 69.2%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Procedure

Benzothioamide (1.37 g, 10 mmol) and benzylbromide (1.71 g, 10 mmol) in dry THF were heated to 60° C. for 2 h. After it was allowed to cool to room temperature, the reaction mixture was filtered. The desired benzyl benzimidothioate hydrobromide as a white solid (2 g, 65%) without further purification. To a solution of benzyl benzimidothioate hydrobromide (1.54 g, 5 mmol) in dry CHCl3 was added in one portion dry pyridine (5 mmol) at ambient temperature followed by ethyl 2-amino-2-cyanoacetate (0.64 g, 5 mmol). The reaction mixture was then heated to 65° C. for 2 h. After cooling to room temperature, the mixture was filtered to give the ethyl 5-amino-2-phenyl-1H-imidazole-4-carboxylate as a yellow colored solid (0.8 g, 68%). This solid (0.46 g, 2 mmol) was added with dry THF, Boc2O (0.87 g, 4 mmol), DMAP (24 mg, 0.2 mmol). The reaction was heated to 65° C. for 5 h. The solvent was evaporated in vacuo to give crude product. This crude product was then dissolved in MeOH—H2O (30 mL, 1:1) and LiOH was added in one portion. The reaction mixture was heated at 70° C. until starting material disappeared by TLC (˜4 h). The mixture was then cooled to ˜0-4° C. and 1N aq HCl was added cautiously dropwise until pH ˜5. The resulted mixture was extracted with DCM (3×20 mL). Combined organic layers were washed with brine (2×20 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by prep-HPLC. The desired product 5-(tert-butoxycarbonylamino)-2-phenyl-1H-imidazole-4-carboxylic acid was obtained as white solid (0.1 g, 16%). 1H-NMR (DMSO, 500 MHz) δ (ppm): 9.01 (s, 1H), 8.05 (s, 2H), 7.35-7.42 (m, 3H), 1.45 (s, 9H); MS (ESI) m/z: 304 [M+H+].

Workup

  1. filtrationthe reaction mixture was filtered
  2. customThe desired benzyl benzimidothioate hydrobromide as a white solid (2 g, 65%) without further purification
  3. temperatureThe reaction mixture was then heated to 65° C. for 2 h
  4. temperatureAfter cooling to room temperature
  5. filtrationthe mixture was filtered

Sources & evidence

ORD record
ord-cace31b84f3745c5b9720f8439af8b83
Source dataset
uspto-grants-2013_05
Patent number
US08435976B2

Reaction notes

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