Sodium Carbonate → N-[(3S)-1-Azabicyclo[2.2.2]oct-3-yl]-7-(2-methoxyphenyl)-1-benzothiophene-2-carboxamide hydrochloride

HRID 2179646Notes

Reaction equation

C(=O)([O-])[O-].[Na+].[Na+].[ClH:7].[N:8]12[CH2:15][CH2:14][CH:11]([CH2:12][CH2:13]1)[C@H:10]([NH:16][C:17]([C:19]1[S:20][C:21]3[C:27](Br)=[CH:26][CH:25]=[CH:24][C:22]=3[CH:23]=1)=[O:18])[CH2:9]2.[CH3:29][O:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1B(O)O>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[ClH:7].[N:8]12[CH2:15][CH2:14][CH:11]([CH2:12][CH2:13]1)[C@H:10]([NH:16][C:17]([C:19]1[S:20][C:21]3[C:27]([C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=4[O:30][CH3:29])=[CH:26][CH:25]=[CH:24][C:22]=3[CH:23]=1)=[O:18])[CH2:9]2

Participants

Conditions

Temperature: 70 °C

Procedure

0.67 ml of 2 M sodium carbonate solution and 18.3 mg (0.02 mmol) of PdCl2(dppf) are added to a mixture of 200 mg (0.45 mmol) of N-[(3S)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzothiophene-2-carboxamide hydrochloride (Example 22A) and 68.1 mg (0.45 mmol) of 2-methoxyphenylboronic acid in 2 ml of DMF. The reaction mixture is heated at 70° C. for 17 h and, after cooling, filtered through kieselguhr and purified by preparative HPLC. The product fractions are concentrated, taken up in a 5:1 mixture of methanol and 1N hydrochloric acid and again concentrated. Drying under high vacuum results in 112 mg (58% of theory) of the title compound.

Workup

temperatureafter cooling
filtrationfiltered through kieselguhr
custompurified by preparative HPLC
concentrationThe product fractions are concentrated
additiontaken up in a 5:1 mixture of methanol and 1N hydrochloric acid
concentrationagain concentrated
customDrying under high vacuum

Sources & evidence

ORD record: ord-b5dea6d1934340878d3b23404aa6289a
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09067931B2

Reaction notes

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