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

HRID 449999Notes

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-1030cd2aa73f4544a5c7107d88eb0b2f
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08486937B2

Reaction notes

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