Triethylamine → N-Cyclopropyl-2-(3-methyl-4-oxo-3,4-dihydroimidazo[5,1-d][1, 2, 3, 5]tetrazin-8-yl)thiazole-4-carboxamide

HRID 570930Notes

Reaction equation

HRID 570930 reaction equation
[NH:1]=[C:2]([C:10]1[N:11]=[CH:12][N:13]2[C:18](=[O:19])[N:17]([CH3:20])[N:16]=[N:15][C:14]=12)[S:3][CH2:4][C:5](=O)[C:6]([OH:8])=O.ClC(OCC(C)C)=O.C(N(CC)CC)C.[CH:36]1([NH2:39])[CH2:38][CH2:37]1>C1COCC1>[CH:36]1([NH:39][C:6]([C:5]2[N:1]=[C:2]([C:10]3[N:11]=[CH:12][N:13]4[C:18](=[O:19])[N:17]([CH3:20])[N:16]=[N:15][C:14]=34)[S:3][CH:4]=2)=[O:8])[CH2:38][CH2:37]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 69828CyclopropylamineHCID 668316143-(Imino(3-methyl-4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazin-8-yl)methylthio)-2-oxopropanoic acid

Product 1

HCID 49870249N-Cyclopropyl-2-(3-methyl-4-oxo-3,4-dihydroimidazo[5,1-d][1, 2, 3, 5]tetrazin-8-yl)thiazole-4-carboxamideYield 49%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-(imino(3-methyl-4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazin-8-yl)methylthio)-2-oxopropanoic acid (0.500 g; 1.8 mmol) in dry THF (30 mL) under nitrogen was added isobutyl chloroformate (0.47 mL; 3.6 mmol), followed by triethylamine (0.51 mL; 3.6 mmol). The mixture was stirred for 1 hours, and then cyclopropylamine (0.206 g; 3.6 mmol) was added, and stirring continued for a further 3 hours. The precipitate was filtered, washed with water (5×20 mL) and diethyl ether (2×15 mL) to yield the title compound as a pale yellow solid (0.278 g; 49%). δH (DMSO-d6) 8.94 (1H, s), 8.41 (1H, s), 8.22 (1H, d, J=4.3), 3.89 (3H, s), 2.88 (1H, m), 0.66-0.76 (4H, m).

Workup

  1. stirringstirring
  2. waitcontinued for a further 3 hours
  3. filtrationThe precipitate was filtered
  4. washwashed with water (5×20 mL) and diethyl ether (2×15 mL)

Sources & evidence

ORD record
ord-0d9889cdbfa040259100853e735701ec
Source dataset
uspto-grants-2015_05
Patent number
US09024018B2

Reaction notes

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