Isopropyl chloroformate → N,N-Dimethyl (8-Carbamoyl-oxoimidazo[5,1-d][1,2,3,5]tetrazin-3(4H)-yl)ethanamide

HRID 2098282Notes

Reaction equation

HRID 2098282 reaction equation
ClC(OC(C)C)=O.[CH3:8][N:9]1CCOC[CH2:10]1.[C:15]([C:18]1[N:19]=[CH:20][N:21]2[C:26](=[O:27])[N:25]([CH2:28][C:29]([OH:31])=O)[N:24]=[N:23][C:22]=12)(=[O:17])[NH2:16].Cl.CNC.C(N(CC)CC)C>CN(C)C=O.CCOCC>[CH3:8][N:9]([CH3:10])[C:29](=[O:31])[CH2:28][N:25]1[C:26](=[O:27])[N:21]2[CH:20]=[N:19][C:18]([C:15](=[O:17])[NH2:16])=[C:22]2[N:23]=[N:24]1

Participants

8

Reactant 5

HCID 7917Isopropyl chloroformateHCID 79724-MethylmorpholineHCID 8471TriethylamineHCID 10473Dimethylamine, hydrochlorideHCID 118314662-(8-Carbamoyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazin-3(4H)-yl)acetic acid

Product 1

HCID 44128649N,N-Dimethyl (8-Carbamoyl-oxoimidazo[5,1-d][1,2,3,5]tetrazin-3(4H)-yl)ethanamide

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent2×

Procedure

Isopropyl chloroformate (1 M in toluene, 1.155 mL, 1.155 mmol) then N-methyl morpholine (0.127 mL, 1.155 mmol) were added to a stirred solution of 2-(8-carbamoyl-oxoimidazo[5,1-d][1,2,3,5]tetrazin-3(4H)-yl)ethanoic acid (0.25 g, 1.050 mmol) in dimethylformamide (1.34 mL) under nitrogen at −10° C. to −15° C. After 1 hour, dimethylamine hydrochloride (0.171 g, 2.100 mmol) and then triethylamine (0.292 mL, 2.100 mmol) in dimethylformamide (0.1 mL) were added. The reaction mixture was stirred at −10° C. to −15° C. for one hour then allowed to warm to room temperature. After 40 hours, ether (5 mL) was added and the resulting precipitate was washed with ether (2×5 mL), acetonitrile (2×5 mL), dichloromethane (2×5 mL) and ether (2×5 mL) then purified by flash column chromatography (SiO2, 9:1 acetonitrile/dichloromethane) and preparative HPLC to furnish the title compound. Yield: 23 mg, 0.082 mmol, 8%. LCMS (ES+) m/z 266 (M+H)+ at 0.80 minutes. 1H NMR (400 MHz, d6-DMSO) δ: 8.89 (1H, s), 7.86 (1H, br s), 7.72 (1H, bs), 5.33 (2H, s), 3.10 (3H, s), 2.86 (3H, s).

Workup

  1. waitAfter 40 hours
  2. washthe resulting precipitate was washed with ether (2×5 mL), acetonitrile (2×5 mL), dichloromethane (2×5 mL) and ether (2×5 mL)
  3. customthen purified by flash column chromatography (SiO2, 9:1 acetonitrile/dichloromethane) and preparative HPLC

Sources & evidence

ORD record
ord-c91c59faaebd4e75a4316a3dde7a5d91
Source dataset
uspto-grants-2013_05
Patent number
US08450479B2

Reaction notes

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