Sodium Carbonate → 3-(2-{[(3R)-1-Azabicyclo[2.2.2]oct-3-ylamino]carbonyl}-1-benzofuran-7-yl)-benzoic acid hydrochloride

HRID 1012810Notes

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[O: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]([C:32]1[CH:33]=[C:34](B(O)O)[CH:35]=[CH:36][CH:37]=1)([OH:31])=[O:30]>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[O:20][C:21]3[C:27]([C:36]4[CH:37]=[C:32]([CH:33]=[CH:34][CH:35]=4)[C:29]([OH:31])=[O:30])=[CH:26][CH:25]=[CH:24][C:22]=3[CH:23]=1)=[O:18])[CH2:9]2

Participants

Conditions

Temperature: 90 °C

Procedure

4.3 ml of 2 M aqueous sodium carbonate solution and 116.9 mg (0.14 mmol) of PdCl2(dppf) are added to a mixture of 1104 mg (2.86 mmol) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzofuran-2-carboxamide hydrochloride (Example 30A) and 475 mg (2.86 mmol) of 3-carboxyphenylboronic acid in 10 ml of DMF. The reaction mixture is heated at 90° C. for 18 h and then filtered through kieselguhr and evaporated to dryness. Purification of the crude product by preparative HPLC, subsequent addition of a 3:1 mixture of acetonitrile and 1N hydrochloric acid, concentrating and drying under high vacuum result in 724 mg (59.2% of theory) of the title compound.

Workup

filtrationfiltered through kieselguhr
customevaporated to dryness
customPurification of the crude product
additionby preparative HPLC, subsequent addition of a 3:1 mixture of acetonitrile and 1N hydrochloric acid
concentrationconcentrating
customdrying under high vacuum

Sources & evidence

ORD record: ord-34c66f6597c747d097d44fb0f3745233
Source dataset: uspto-grants-2011_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07977485B2

Reaction notes

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