Sulfuric Acid → HCID 178496565, compound

HRID 454330Notes

Reaction equation

HRID 454330 reaction equation
CO[C@H]1CC[C@H](C[N:10]2C(=O)CNC3N=CC(C4C(C)=CC(C(N)=O)=NC=4)=[N:20][C:11]2=3)CC1.[CH3:31][O:32][C@H:33]1[CH2:38][CH2:37][C@H:36]([CH2:39][N:40]2[C:45](=[O:46])[CH2:44][NH:43][C:42]3[N:47]=[CH:48][C:49]([C:51]4[C:52]([CH3:59])=[CH:53][C:54]([C:57]#[N:58])=[N:55][CH:56]=4)=[N:50][C:41]2=3)[CH2:35][CH2:34]1.FC(F)(F)C(O)=O.S(=O)(=O)(O)O.C(=O)([O-])[O-].[Na+].[Na+]>>[CH3:31][O:32][C@H:33]1[CH2:38][CH2:37][C@H:36]([CH2:39][N:40]2[C:41]3=[N:50][C:49]([C:51]4[CH:56]=[N:55][C:54]([C:57]5[N:20]=[CH:11][NH:10][N:58]=5)=[CH:53][C:52]=4[CH3:59])=[CH:48][N:47]=[C:42]3[NH:43][CH2:44][C:45]2=[O:46])[CH2:35][CH2:34]1

Participants

6

Reactant 5

HCID 1118Sulfuric AcidHCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 178496566HCID 178496566, compoundHCID 178496567HCID 178496567, compound

Product 1

HCID 178496565HCID 178496565, compoundYield 67%

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-methylpicolinamide. 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

  1. customReaction pH
  2. extractionthe resulting solution was extracted with ethyl acetate (3×15 mL)
  3. customOrganic layers were collected
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. custompurified
  7. customreverse-phase preparatory HPLC (10-100% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min)
  8. customcondensed under reduced pressure
  9. customdried under high vacuum

Sources & evidence

ORD record
ord-de99d449512e43ebb4a87d30bb7cb399
Source dataset
uspto-grants-2013_07
Patent number
US08492381B2

Reaction notes

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