Cesium carbonate → N-[(3S)-1-Azabicyclo[2.2.2]oct-3-yl]-6-{[2-(propylamino)ethyl]amino}-1,2-benzisothiazole-3-carboxamide

HRID 2362858Notes

Reaction equation

C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P([C:41]2[CH:46]=[CH:45]C=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[N:47]12[CH2:54][CH2:53][CH:50]([CH2:51][CH2:52]1)[C@H:49]([NH:55][C:56]([C:58]1[C:62]3[CH:63]=[CH:64][C:65](Br)=[CH:66][C:61]=3[S:60][N:59]=1)=[O:57])[CH2:48]2.C(=O)([O-])[O-].[Cs+].[Cs+].N1CCCC1=O.C[N:81]1[CH2:85][CH2:84][NH:83]C1=O>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N:47]12[CH2:54][CH2:53][CH:50]([CH2:51][CH2:52]1)[C@H:49]([NH:55][C:56]([C:58]1[C:62]3[CH:63]=[CH:64][C:65]([NH:81][CH2:85][CH2:84][NH:83][CH2:45][CH2:46][CH3:41])=[CH:66][C:61]=3[S:60][N:59]=1)=[O:57])[CH2:48]2

Participants

Conditions

Temperature: 100 °C

Procedure

Palladium (II) acetate (0.09 mmol) was added to a solution of (R)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.14 mmol) in toluene (8 mL) and the reaction mixture was maintained until the contents completely dissolved. The resultant yellow solution was transferred to a mixture of N-[(3S)-1-azabicyclo[2.2.2]oct-3-yl]-6-bromo-1,2-benzisothiazole-3-carboxamide (0.33 mmol), cesium carbonate (0.39 mmol) and 1-methyl-2-imidazolidinone 2-pyrrolidinone (0.500 mmol) under an atmosphere of nitrogen gas and the reaction mixture was heated at 100° C. for 16 h. The reaction mixture was filtered through Celite and concentrated. The residue was purified by HPLC, thus providing the product in 70% yield.

Workup

temperaturethe reaction mixture was maintained until the contents
dissolutioncompletely dissolved
filtrationThe reaction mixture was filtered through Celite
concentrationconcentrated
customThe residue was purified by HPLC
customthus providing the product in 70% yield

Sources & evidence

ORD record: ord-cee1c0458c464293ac21f821f08e6064
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08691841B2

Reaction notes

Loading…