Hydrochloric Acid → 2H-benzo-furo[2,3-a]quinolizine-2-carbonitrile

HRID 1481498Notes

Reaction equation

HRID 1481498 reaction equation
Cl.Cl.C([CH:5]1[C@@H:14]2[N:9]([CH2:10][CH2:11][C:12]3[C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=4[O:15][C:13]=32)[CH2:8][CH2:7][C@H:6]1NCCCS(N)(=O)=O)#N.[C:30](N1C=CN=C1)([N:32]1C=CN=C1)=O.Cl>>[CH:5]1[CH:6]([C:30]#[N:32])[CH:7]=[CH:8][N:9]2[C:14]=1[C:13]1[O:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:12]=1[CH:11]=[CH:10]2

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 121393552(2R,12bS)-[2-[(cyano-1,3,4,6,7,12b-hexahydrobenzofuro-[2,3-a]quinolizine-2-yl)-amino]-ethyl]methanesulfon-amide dihydrochloride

Product 1

HCID 1317366402H-benzo-furo[2,3-a]quinolizine-2-carbonitrile

Procedure

The process of the invention for the manufacture of N-(2-((2R,12bS)-2′-oxo-1,3,4,6,7,12b-hexahydrospiro[benzofuro[2,3-a]quinolizine-2,4′-imidazolidine]-3′-yl)ethyl)-methanesulfon-amide having the formula I comprises the steps, where in the first step (S)-1,3,4,6,7,12b-hexahydro-2H-benzo[b]furo[2,3-a]quinolizin-2-one of formula II and N-(2-aminoethyl)methanesulfonamide of formula III are contacted with trimethylsilyl cyanide in the presence of an agent capable of capturing water molecules, in an organic solvent, followed by adding hydrogen chloride to obtain (2R,12bS)-[2-[(cyano-1,3,4,6,7,12b-hexahydrobenzofuro-[2,3-a]quinolizine-2-yl)-amino]ethyl]methanesulfon-amide dihydrochloride, in the second step (2R,12bS)-[2-[(cyano-1,3,4,6,7,12b-hexahydrobenzofuro-[2,3-a]quinolizine-2-yl)-amino]-ethyl]methanesulfonamide dihydrochloride is contacted with 1,1′-carbonyldiimidazole in the presence of a hydrogen chloride acceptor in an organic solvent to obtain (2R,12bS)-1,3,4,6,7,12b-hexahydro-[2,3-methylsulfonyl)-2-oxo-1-imidazolidinyl]-2H-benzo-furo[2,3-a]quinolizine-2-carbonitrile, and in the third step (2R,12bS)-1,3,4,6,7,12b-hexahydro-[2,3-methylsulfonyl)-2-oxo-1-imidazolidinyl]-2H-benzofuro[2,3-a]quinolizine-2-carbonitrile is contacted with hydrogen in the presence of Raney nickel catalyst and sodium methoxide or potassium tert-butoxide in methanol solvent to yield N-(2-((2R,12bS)-2′-oxo-1,3,4,6,7,12b-hexa-hydrospiro-[benzofuro[2,3-a]quinolizine-2,4′-imidazolidine]-3′-yl)ethyl)-methanesulfonamide.

Sources & evidence

ORD record
ord-0b714874e2d541df8170902ecded1787
Source dataset
uspto-grants-2016_08
Patent number
US09409919B2

Reaction notes

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