Triethylamine → HCID 86674651, compound

HRID 245697Notes

Reaction equation

HRID 245697 reaction equation
Cl[C:2](OC(Cl)(Cl)Cl)=[O:3].[O:9]1[C:13]2([CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)[O:12][CH2:11][CH2:10]1.C(N(CC)C(C)C)(C)C.Cl.[NH2:29][CH2:30][C:31]1[C:36]([Cl:37])=[N:35][CH:34]=[CH:33][N:32]=1.C(N(CC)CC)C>C(OCC)(=O)C.O>[Cl:37][C:36]1[C:31]([CH2:30][NH:29][C:2]([N:16]2[CH2:17][CH2:18][C:13]3([O:12][CH2:11][CH2:10][O:9]3)[CH2:14][CH2:15]2)=[O:3])=[N:32][CH:33]=[CH:34][N:35]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 10426DiphosgeneHCID 674351,4-Dioxa-8-azaspiro(4.5)decaneHCID 81531DiisopropylethylamineHCID 42614233(3-Chloropyrazin-2-yl)methanamine hydrochloride

Product 1

HCID 86674651HCID 86674651, compoundYield 114.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To trichloromethyl chloroformate (4.19 mmol, 0.505 ml) in ethyl acetate (5 ml) at 0° C. was added dropwise 1,4-dioxa-8-azaspiro[4.5]decane (6.98 mmol, 0.895 ml) in ethyl acetate (5 ml) and N,N-diisopropylethylamine (6.98 mmol, 1.217 ml). After one hour the mixture was concentrated, the residue was dissolved in dichloromethane (25 ml) and 2-aminomethyl-3-chloropyrazine hydrochloride (content 60%; 10.00 mmol, 3 g) and triethylamine (27.9 mmol, 3.89 ml) were added. After stirring for 16 hours at room temperature the reaction mixture was diluted with water, filtered over decalite, washed with water, filtered over a phase separation filter and concentrated in vacuo. The crude product was dissolved in dichloromethane containing 1% triethylamine and purification by column chromatography (silica gel; dichloromethane containing 1% triethylamine) gave N-((3-chloropyrazin-2-yl)methyl)-1,4-dioxa-8-azaspiro[4.5]decane-8-carboxamide (1.5 g).

Workup

  1. concentrationAfter one hour the mixture was concentrated
  2. dissolutionthe residue was dissolved in dichloromethane (25 ml)
  3. filtrationfiltered over decalite
  4. washwashed with water
  5. filtrationfiltered over a phase separation
  6. filtrationfilter
  7. concentrationconcentrated in vacuo
  8. dissolutionThe crude product was dissolved in dichloromethane containing 1% triethylamine
  9. custompurification by column chromatography (silica gel; dichloromethane containing 1% triethylamine)

Sources & evidence

ORD record
ord-52d71f02e10a445e93c7799f69ed773a
Source dataset
uspto-grants-2014_02
Patent number
US08658794B2

Reaction notes

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