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

HRID 1012733Notes

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:32]=[C:33](B(O)O)[CH:34]=[CH:35][CH:36]=1>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:35]4[CH:34]=[CH:33][CH:32]=[C:31]([O:30][CH3:29])[CH:36]=4)=[CH:26][CH:25]=[CH:24][C:22]=3[CH:23]=1)=[O:18])[CH2:9]2

Participants

Conditions

Temperature: 80 °C

Procedure

0.16 ml of 2 M aqueous sodium carbonate solution and 4.2 mg (0.005 mmol) of PdCl2(dppf) are added to a mixture of 49 mg (0.10 mmol) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzothiophene-2-carboxamide hydrochloride (Example 8A) and 15.8 mg (0.10 mmol) of 3-methoxyphenylboronic acid in 1 ml of DMF. The reaction mixture is heated at 80° C. for 14 h, then filtered through kieselguhr and evaporated to dryness. Purification of the crude product by preparative HPLC, subsequent addition of 1N hydrochloric acid and drying under high vacuum result in 8.0 mg (18% of theory) of the title compound.

Workup

filtrationfiltered through kieselguhr
customevaporated to dryness
customPurification of the crude product
additionby preparative HPLC, subsequent addition of 1N hydrochloric acid
customdrying under high vacuum

Sources & evidence

ORD record: ord-a8d840fed1424d9bb844699d6403cd9f
Source dataset: uspto-grants-2011_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07977485B2

Reaction notes

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