Hydrochloric Acid → 2-(2,4-Dichlorophenyl)-5-(1-(2-(pyrrolidin-1-yl)ethyl)-1H-indazol-5-yl)furo[3,2-c]pyridin-4(5H)-one Hydrochloride

HRID 422090Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[O:17][C:16]2[CH:15]=[CH:14][N:13]([C:18]3[CH:19]=[C:20]4[C:24](=[CH:25][CH:26]=3)[N:23]([CH2:27][CH2:28][N:29]3[CH2:33][CH2:32][CH2:31][CH2:30]3)[N:22]=[CH:21]4)[C:12](=[O:34])[C:11]=2[CH:10]=1.Cl.C(OCC)C>C(Cl)Cl>[ClH:1].[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[O:17][C:16]2[CH:15]=[CH:14][N:13]([C:18]3[CH:19]=[C:20]4[C:24](=[CH:25][CH:26]=3)[N:23]([CH2:27][CH2:28][N:29]3[CH2:30][CH2:31][CH2:32][CH2:33]3)[N:22]=[CH:21]4)[C:12](=[O:34])[C:11]=2[CH:10]=1

Participants

Conditions

Temperature: 25 °C

Procedure

2-Bromo-5-(1-(2-(pyrrolidin-1-yl)ethyl)-1H-indazol-5-yl)furo[3,2-c]pyridin-4(5H)-one (73 mg, 0.17 mmol), 2,4-dichlorophenylboronic acid (36 mg, 0.19 mmol), K2CO3 (47 mg, 0.34 mmol) and Pd(PPh3)2Cl2 (12 mg, 0.017 mmol) were diluted with anhydrous DMSO (4 mL) and the resulting suspension was degassed under reduced pressure for 45 min. The suspension was place under an atmosphere of Ar and heated to 95° C. for 1.75 h. The suspension was cooled and H2O was added. The aqueous suspension was filtered, the solid was diluted with CH2Cl2 and the resulting solution was dried over Na2SO4 and concentrated under reduced pressure to afford 50 mg of a pink solid. Flash chromatography on silica gel [9:1 Et2O/(4:1 MeOH/Et3N)] yielded 24 mg (29%) of 2-(2,4-dichlorophenyl)-5-(1-(2-(pyrrolidin-1-yl)ethyl)-1H-indazol-5-yl)furo[3,2-c]pyridin-4(5H)-one as a white powder. A solution of 2-(2,4-dichlorophenyl)-5-(1-(2-(pyrrolidin-1-yl)ethyl)-1H-indazol-5-yl)furo[3,2-c]pyridin-4(5H)-one (17 mg, 0.035 mmol) in CH2Cl2 (5 mL) was treated with anhydrous HCl in diethyl ether (0.04 mL, 0.04 mmol, 1.0 M) and the resulting solution was stirred at 25° C. for 1 h. The solution was concentrated under reduced pressure with Et2O to afford the title compound as a white powder: mp 258-260° C.; 1H NMR (500 MHz, DMSO-d6) δ 9.74-9.82 (br s, 1H, NH), 8.29 (s, 1H), 7.99 (d, J=8.5 Hz, 1H), 7.92-7.87 (m, 2H), 7.84 (d, J=2.0 Hz, 1H), 7.74 (d, J=7.5 Hz, 1H), 7.63 (dd, J=8.5, 2.0 Hz, 1H), 7.59 (s, 1H), 7.53 (br d, J=9.5 Hz, 1H), 6.94 (d, J=7.5 Hz, 1H), 4.87 (t, J=5.5 Hz, 2H), 3.80-3.70 (m, 2H), 3.61-3.52 (m, 2H), 3.15-3.02 (m, 2H), 2.08-1.92 (m, 2H), 1.90-1.79 (m, 2H); ESI MS m/z 493 [M+H]+.

Workup

concentrationThe solution was concentrated under reduced pressure with Et2O

Sources & evidence

ORD record: ord-287b77c989134b7f92144eaf3f1b5556
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08101632B2

Reaction notes

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