Hydrochloric Acid → (N-1-Azabicyclo[2.2.2]oct-3-yl)-8-chloro-5-methoxy-1,2,3,4-tetrahydrobenzo-1,4-diazine-6-carboxamide

HRID 2107317Notes

Reaction equation

[C:1]([C:4]1[CH:13]=[C:12]([Cl:14])[C:7]2[NH:8][CH2:9][CH2:10][NH:11][C:6]=2[C:5]=1[O:15][CH3:16])([OH:3])=O.CC[N:19](CC)CC.ClC(OCC)=O.N[CH:31]1[CH2:36][CH:35]2[CH2:37][CH2:38][N:32]1[CH2:33][CH2:34]2.C([O-])([O-])=O.[K+].[K+].Cl>C(Cl)(Cl)Cl.O.CCO>[N:32]12[CH2:38][CH2:37][CH:35]([CH2:34][CH2:33]1)[CH:36]([NH:19][C:1]([C:4]1[CH:13]=[C:12]([Cl:14])[C:7]3[NH:8][CH2:9][CH2:10][NH:11][C:6]=3[C:5]=1[O:15][CH3:16])=[O:3])[CH2:31]2

Participants

Conditions

Temperature: -23 °C

Procedure

The carboxylic acid of step 7 above (3.71 mmoles) is dissolved in CHCl3 (10 ml), combined with Et3N (3.71 mmoles), cooled to -23° C. and mixed with ethyl chloroformate (3.71 mmoles) for 30 minutes. Aminoquinuclidine (14.8 mmoles) and aqueous K2CO3 (1 ml) are added and the reaction mixture is stirred for 1 hour and diluted with H2O (10 ml). The organic layer is separated, washed with aqueous NaHCO3 (50 ml, sat'd) and H2O (3×50 ml), dried, evaporated and chromatographed with Ether:MeOH (5 g, 1:1) to give a brown oil which is dissolved in EtOH. Concentrated HCl is added to the solution precipitating a white solid which is filtered and recrystallized affording a white solid which NMR indicates is the desired product.

Workup

customThe organic layer is separated
washwashed with aqueous NaHCO3 (50 ml, sat'd) and H2O (3×50 ml)
customdried
customevaporated
customchromatographed with Ether
customMeOH (5 g, 1:1) to give a brown oil which
customprecipitating a white solid which
filtrationis filtered
customrecrystallized
customaffording a white solid which NMR

Sources & evidence

ORD record: ord-9082b55dc3b246d7903dd82b8610f644
Source dataset: uspto-grants-1990_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04933445

Reaction notes

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