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

HRID 1012732Notes

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

Participants

Conditions

Temperature: 80 °C

Procedure

0.14 ml of 2 M aqueous sodium carbonate solution and 5.7 mg (0.007 mmol) of PdCl2(dppf) are added to a mixture of 56 mg (0.14 mmol) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzothiophene-2-carboxamide hydrochloride (Example 8A) and 18.7 mg (0.15 mmol) of phenylboronic acid in 1 ml of DMF. The reaction mixture is heated to 80° C. After 3 h at this temperature, a further 5.7 mg (0.007 mmol) of PdCl2(dppf) are added, and the mixture is stirred at 80° C. for a further 12 h. The reaction mixture is 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 10.6 mg (18% of theory) of the title compound.

Workup

filtrationThe reaction mixture is filtered 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-cf9f1c0b20a74ae69036884c75435a0e
Source dataset: uspto-grants-2011_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07977485B2

Reaction notes

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