Hydrochloric Acid → 3-[(1S,2S)-2-aminocyclohexyl]-6-[(6-chloropyridin-3-yl)methyl]benzo[h]quinazolin-4(3H)-one

HRID 1042305Notes

Reaction equation

C(OC(=O)[NH:7][C@H:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@@H:9]1[N:14]1[C:23](=[O:24])[C:22]2[C:17](=[C:18]3[CH:36]=[CH:35][CH:34]=[CH:33][C:19]3=[C:20]([CH2:25][C:26]3[CH:27]=[N:28][C:29]([Cl:32])=[CH:30][CH:31]=3)[CH:21]=2)[N:16]=[CH:15]1)(C)(C)C.Cl>CO>[NH2:7][C@H:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@@H:9]1[N:14]1[C:23](=[O:24])[C:22]2[C:17](=[C:18]3[CH:36]=[CH:35][CH:34]=[CH:33][C:19]3=[C:20]([CH2:25][C:26]3[CH:27]=[N:28][C:29]([Cl:32])=[CH:30][CH:31]=3)[CH:21]=2)[N:16]=[CH:15]1

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of tert-butyl{(1S,2S)-2-[6-[(6-chloropyridin-3-yl)methyl]-4-oxobenzo[h]quinazolin-3(4H)-yl]cyclohexyl}carbamate (0.080 g, 0.15 mmol) in 2 mL of methanol was added hydrochloric acid (0.15 mL, 6 N aqueous, 0.92 mmol). The reaction was heated at 60° C. for 2 h, cooled to ambient temperature and concentrated in vacuo. The residue was concentrated twice with toluene. The residue was purified via preparative reverse phase HPLC to provide 3-[(1S,2S)-2-aminocyclohexyl]-6-[(6-chloropyridin-3-yl)methyl]benzo[h]quinazolin-4(3H)-one that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 419.0 for [M+H]+: 1H NMR (400 MHz, d6-DMSO) δ 9.10-9.08 (m, 1H), 8.56 (br s, 1H), 8.27 (s, 1H), 8.14-8.12 (m, 1H), 8.04 (s, 1H), 7.80-7.75 (m, 3H), 7.43-7.36 (m, 1H), 4.60 (s, 2H), 2.31-2.24 (m, 2H), 2.12-1.94 (m, 4H), 1.70-1.56 (m, 4H).

Workup

temperaturecooled to ambient temperature
concentrationconcentrated in vacuo
concentrationThe residue was concentrated twice with toluene
customThe residue was purified via preparative reverse phase HPLC

Sources & evidence

ORD record: ord-6ad7abbf9fc64da5b2aa7015491986bd
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08557832B2

Reaction notes

Loading…