Cesium carbonate → 4-Chloro-3'-(2-cyclopentyl-1-oxoisoindolin-5-yl)biphenyl-3-carboxylic acid

HRID 404961Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[N:6]([CH:12]1[CH2:16][CH2:15][CH2:14][CH2:13]1)[CH2:5]2.B([C:20]1[CH:21]=[C:22]([C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[C:28]([C:33]([OH:35])=[O:34])[CH:27]=2)[CH:23]=[CH:24][CH:25]=1)(O)O.C([O-])([O-])=O.[Cs+].[Cs+]>COCCOC.O.CCO.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:32][C:29]1[CH:30]=[CH:31][C:26]([C:22]2[CH:23]=[CH:24][CH:25]=[C:20]([C:2]3[CH:3]=[C:4]4[C:8](=[CH:9][CH:10]=3)[C:7](=[O:11])[N:6]([CH:12]3[CH2:16][CH2:15][CH2:14][CH2:13]3)[CH2:5]4)[CH:21]=2)=[CH:27][C:28]=1[C:33]([OH:35])=[O:34]

Participants

Conditions

Temperature: 75 °C

Procedure

5-Bromo-2-cyclopentylisoindolin-1-one (76 mg, 0.27 mmol), 3′-borono-4-chlorobiphenyl-3-carboxylic acid (90 mg, 0.33 mmol), Cs2CO3 (268 mg, 0.82 mmol) and PdCl2(PPh3)2 (22 mg, 0.03 mmol), were dissolved in a mixture of DME-H2O-EtOH (9.1 mL:3 mL:2.2 mL) and heated at 75° C. for 2 hours. The mixture was filtered through celite washed with water and filtrate was acidified with 2.5 M HCl to form the crude acid as a yellow solid. The crude residue was purified using automated prep-HPLC to yield the desired compound (14.3 mg, 12%) as a pale yellow solid. 1H NMR (400 MHz, CDCl3): δ 8.24 (d, J=2.3 Hz, 1H), 7.94 (d, J=8.0 Hz, 1H), 7.78-7.54 (m, 8H), 4.84-4.75 (m, 1H), 4.43 (s, 2H), 2.08-2.00 (m, 2H), 1.83-1.62 (m, 6H). LRMS calcd. for C26H22ClNO3 [M+H]+ 432 found: 432.

Workup

filtrationThe mixture was filtered through celite
washwashed with water and filtrate
customto form the crude acid as a yellow solid
customThe crude residue was purified

Sources & evidence

ORD record: ord-4fb36a2c42af493d98b67993f3f91242
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08748632B2

Reaction notes

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