Hydrochloric Acid → HCID 178423524, compound

HRID 1890826Notes

Reaction equation

HRID 1890826 reaction equation
Cl.[CH3:2][C:3]1([CH3:40])[C:30](=[O:31])[NH:29][C:6]2=[N:7][CH:8]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([C:17]4[N:21](C5CCCCO5)[CH:20]=[N:19][N:18]=4)=[CH:13][C:12]=3[CH3:28])[N:10]=[C:5]2[N:4]1[CH2:32][CH2:33][CH:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1>O.C(O)C>[CH3:2][C:3]1([CH3:40])[C:30](=[O:31])[NH:29][C:6]2=[N:7][CH:8]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([C:17]4[NH:21][CH:20]=[N:19][N:18]=4)=[CH:13][C:12]=3[CH3:28])[N:10]=[C:5]2[N:4]1[CH2:32][CH2:33][CH:34]1[CH2:35][CH2:36][O:37][CH2:38][CH2:39]1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 533752293,3-Dimethyl-6-(2-methyl-4-(4-(tetrahydro-2H-pyran-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-4-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

Product 1

HCID 178423524HCID 178423524, compoundYield 48%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

6 N Hydrochloric acid in water was added to a stirred mixture of 3,3-dimethyl-6-(2-methyl-4-(4-(tetrahydro-2H-pyran-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-4-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one in ethanol at 80° C. The resulting mixture was stirred vigorously and heated at 80° C. under a reflux condenser under nitrogen for 70 min. The resulting mixture was filtered and purified using reverse-phase preparatory HPLC (10-65% acetonitrile+0.1% TFA in water+0.1% TFA, over 30 min). Fractions containing the desired product were combined, neutralized with saturated aqueous sodium bicarbonate and the acetonitrile removed under reduced pressure. Solids were collected by vacuum filtration, washed thoroughly with water and diethyl ether and dried under high vacuum at 50° C. to give the desired product in 48% yield. 1H NMR (400 MHz, DMSO-d6) δ (ppm) 11.32 (br. s., 1H), 8.44 (br. s., 1H), 7.96 (s, 1H), 7.90 (d, J=8.59 Hz, 1H), 7.70 (s, 1H), 7.56 (d, J=7.81 Hz, 1H), 3.78 (dd, J=2.93, 11.13 Hz, 2H), 3.52-3.64 (m, 2H), 3.23 (t, J=10.93 Hz, 2H), 2.48 (s, 3H), 1.51-1.66 (m, 5H), 1.49 (s, 6H), 1.11-1.26 (m, 2H); MS (ESI) m/z 448.3 [M+1]+.

Workup

  1. filtrationThe resulting mixture was filtered
  2. custompurified
  3. customreverse-phase preparatory HPLC (10-65% acetonitrile+0.1% TFA in water+0.1% TFA, over 30 min)
  4. additionFractions containing the desired product
  5. customthe acetonitrile removed under reduced pressure
  6. filtrationSolids were collected by vacuum filtration
  7. washwashed thoroughly with water and diethyl ether
  8. customdried under high vacuum at 50° C.

Sources & evidence

ORD record
ord-092137ea1a2b470c8c900ab95db1ff1a
Source dataset
uspto-grants-2013_08
Patent number
US08507492B2

Reaction notes

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