HCID 178496583, compound → HCID 178496584, compound

HRID 1890871Notes

Reaction equation

[CH3:1][O:2][C@@H:3]1[CH2:8][CH2:7][C@H:6]([N:9]2[C:18]3[C:13](=[N:14][CH:15]=[C:16]([C:19]4[C:20]([CH3:36])=[N:21][C:22]([C:25]5[N:29](C6CCCCO6)[CH:28]=[N:27][N:26]=5)=[CH:23][CH:24]=4)[N:17]=3)[NH:12][C:11](=[O:37])[CH2:10]2)[CH2:5][CH2:4]1>C(O)C.Cl>[CH3:1][O:2][C@@H:3]1[CH2:8][CH2:7][C@H:6]([N:9]2[C:18]3[C:13](=[N:14][CH:15]=[C:16]([C:19]4[C:20]([CH3:36])=[N:21][C:22]([C:25]5[NH:29][CH:28]=[N:27][N:26]=5)=[CH:23][CH:24]=4)[N:17]=3)[NH:12][C:11](=[O:37])[CH2:10]2)[CH2:5][CH2:4]1

Participants

Conditions

Temperature: 80 °C

Procedure

4-((cis)-4-Methoxycyclohexyl)-6-(2-methyl-6-(4-(tetrahydro-2H-pyran-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one (0.279 g, 0.553 mmol) was diluted with ethanol (15 mL) and hydrogen chloride (4.0 N in dioxanes, 5 mL). The solution was stirred at 75° C. for 1 h and at 80° C. for 2 h. The solution was condensed to a slurry and diluted with ethanol and sonicated. The precipitate was filtered and washed with additional ethanol followed by acetonitrile. The crude solid was purified using reverse-phased semi-preparative HPLC (10-100% acetonitrile+0.1% TFA in water+0.1 TFA, over 30 min) to afford the title compound (0.040 g, 0.095 mmol, 17% yield). 1H NMR (400 MHz, METHANOL-d4) δ (ppm) 7.88-8.13 (m, 2H), 7.65 (s, 1H), 4.58 (s, 1H), 4.16 (s, 2H), 3.47 (br. s., 1H), 3.22-3.32 (m, 66H), 2.73 (s, 3H), 2.08 (br. s., 2H), 1.91 (br. s., 2H), 1.56 (br. s., 4H); MS (ESI) m/z 421.2 [M+1]+; mp 192-195° C.

Workup

customcondensed to a slurry
customsonicated
filtrationThe precipitate was filtered
washwashed with additional ethanol
customThe crude solid was purified
customreverse-phased semi-preparative HPLC (10-100% acetonitrile+0.1% TFA in water+0.1 TFA, over 30 min)

Sources & evidence

ORD record: ord-4fe4463fad16450e81fdb30ee25f9a60
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08507492B2

Reaction notes

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