Acetic Anhydride → HCID 118159271, compound

HRID 713371Notes

Reaction equation

HRID 713371 reaction equation
[CH:1]([NH:4][C:5]1[N:10]=[C:9]2[CH:11]=[N:12][CH:13]=[CH:14][C:8]2=[N:7][C:6]=1[N:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]1)([CH3:3])[CH3:2].[C:28](OC(=O)C)(=[O:30])[CH3:29]>CC(C)=O.O1CCOCC1.[Pd]>[C:28]([N:12]1[CH2:13][CH2:14][C:8]2[C:9](=[N:10][C:5]([NH:4][CH:1]([CH3:3])[CH3:2])=[C:6]([N:15]3[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:25])([CH3:27])[CH3:26])=[O:22])[CH2:17][CH2:16]3)[N:7]=2)[CH2:11]1)(=[O:30])[CH3:29]

Participants

6

Reactant 2

HCID 7918Acetic AnhydrideHCID 118159138HCID 118159138, compound

Product 1

HCID 118159271HCID 118159271, compoundYield 47.5%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 180AcetoneSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
45 °C

Procedure

To a pressure reactor charged with a red-orange solution of tert-butyl 4-(3-(isopropylamino)pyrido[3,4-b]pyrazin-2-yl)piperazine-1-carboxylate (2.0 g, 5.37 mmol) in acetone (100 mL) and dioxane (100 mL) was added palladium, 10 wt % on activated carbon (0.229 g, 2.148 mmol) as a slurry in dioxane (3 mL) under nitrogen. Next, acetic anhydride (5.04 mL, 53.7 mmol) was added at 23° C. The mixture was stirred under hydrogen at 310 kPa for 17 hr at 45° C. The reaction mixture was filtered through Celite™, rinsed with dioxane, and concentrated via rotary evaporation. The crude material was purified via medium pressure chromatography using 10% to 100% gradient of EtOAc in heptane on an NH 60 μM size 400 column (Shoko Scientific Purif-Pack™) to give the title compound (1.068 g, 47.5%) as a yellow foam. 1H NMR (500 MHz, DMSO-d6, mixture of rotamers) 6 ppm 1.16-1.21 (m, 6H), 1.42 (s, 9H), 2.08 (s, 1.3H), 2.09 (s, 1.7H), 2.58 (t, J=5.9 Hz, 0.9H), 2.70 (t, J=5.6 Hz, 1.1H), 2.87-2.98 (m, 4H), 3.51 (br s, 4H), 3.67-3.75 (m, 2H), 4.06-4.15 (m, 1H), 4.41 (s, 1.1H), 4.44 (s, 0.9H), 5.50 (d, J=7.8 Hz, 1H), 5.53 (d, J=7.8 Hz, 1H); ESI-MS m/z [M+H]+ 419.0.

Workup

  1. filtrationThe reaction mixture was filtered through Celite™
  2. washrinsed with dioxane
  3. concentrationconcentrated via rotary evaporation
  4. customThe crude material was purified via medium pressure chromatography

Sources & evidence

ORD record
ord-ec600bded99e45b3b2dbd27c1c3e1827
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

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