Hydrochloric Acid → HCID 121393552, compound

HRID 1481497Notes

Reaction equation

HRID 1481497 reaction equation
O=C1[N:6]([CH2:7][CH2:8]NS(C)(=O)=O)[C@:5]2([CH2:22][C@@H:21]3[N:16]([CH2:17][CH2:18][C:19]4[C:25]5[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=5[O:23][C:20]=43)[CH2:15][CH2:14]2)CN1.NCC[NH:33][S:34]([CH3:37])(=[O:36])=[O:35].C[Si]([C:42]#[N:43])(C)C.[ClH:44]>O>[ClH:44].[ClH:44].[C:42]([CH:14]1[C@@H:15]2[N:16]([CH2:17][CH2:18][C:19]3[C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=4[O:23][C:20]=32)[CH2:21][CH2:22][C@H:5]1[NH:6][CH2:7][CH2:8][CH2:37][S:34]([NH2:33])(=[O:36])=[O:35])#[N:43]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 82115Trimethylsilyl cyanideHCID 163952N-[2-(2'-Hydroxy-1,3,4,6,7,12b-hexahydrospiro[1-benzofuro[2,3-a]quinolizine-2,4'-imidazol]-3'(5'H)-yl)ethyl]methanesulfonamideHCID 533845N-(2-Aminoethyl)methanesulfonamide

Product 1

HCID 121393552HCID 121393552, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

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-12de7e617fc14f72b53f5cc8dbf7daf3
Source dataset
uspto-grants-2016_08
Patent number
US09409919B2

Reaction notes

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