Sulfuric Acid → HCID 178496567, compound
Reaction equation
[CH3:1][O:2][C@H:3]1[CH2:8][CH2:7][C@H:6]([CH2:9][N:10]2[C:15](=[O:16])[CH2:14][NH:13][C:12]3[N:17]=[CH:18][C:19]([C:21]4[C:22]([CH3:29])=[CH:23][C:24]([C:27]#[N:28])=[N:25][CH:26]=4)=[N:20][C:11]2=3)[CH2:5][CH2:4]1.FC(F)(F)C(O)=[O:33].S(=O)(=O)(O)O.C(=O)([O-])[O-].[Na+].[Na+]>>[CH3:1][O:2][C@H:3]1[CH2:8][CH2:7][C@H:6]([CH2:9][N:10]2[C:15](=[O:16])[CH2:14][NH:13][C:12]3[N:17]=[CH:18][C:19]([C:21]4[C:22]([CH3:29])=[CH:23][C:24]([C:27]([NH2:28])=[O:33])=[N:25][CH:26]=4)=[N:20][C:11]2=3)[CH2:5][CH2:4]1Participants
Conditions
- Temperature
- 65 °C
Procedure
5-(8-(((trans)-4-Methoxycyclohexyl)methyl)-7-oxo-5,6,7,8-tetrahydropyrazino[2,3-b]pyrazin-2-yl)-4-methylpicolinonitrile (0.607 g, 1.55 mmol), trifluoroacetic acid (2.0 mL, 26.0 mmol) and sulfuric acid (0.5 mL, 9.38 mmol) were combined and heated at 65° C. for 1 h. Reaction pH was adjusted to 10 with sodium carbonate and the resulting solution was extracted with ethyl acetate (3×15 mL). Organic layers were collected, dried over magnesium sulfate, concentrated and purified using reverse-phase preparatory HPLC (10-100% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min). Clean fractions were combined and condensed under reduced pressure and dried under high vacuum to afford the title compound as a yellow solid (0.425 g, 1.04 mmol, 67% yield). MS (ESI) m/z 411.5 [M+1]+.
Workup
- customReaction pH
- extractionthe resulting solution was extracted with ethyl acetate (3×15 mL)
- customOrganic layers were collected
- dry with materialdried over magnesium sulfate
- concentrationconcentrated
- custompurified
- customreverse-phase preparatory HPLC (10-100% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min)
- customcondensed under reduced pressure
- customdried under high vacuum
Sources & evidence
- ORD record
- ord-29e8c5f9d6ff4e8ba35c43037745c5a0
- Source dataset
- uspto-grants-2013_10
- Patent number
- US08569494B2
Reaction notes
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