Isopropylamine → HCID 118159138, compound

HRID 713206Notes

Reaction equation

HRID 713206 reaction equation
Cl[C:2]1[N:7]=[C:6]2[CH:8]=[N:9][CH:10]=[CH:11][C:5]2=[N:4][C:3]=1[N:12]1[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]1.[F-].[K+].CC[N:29](C(C)C)[CH:30]([CH3:32])[CH3:31].CC(N)C>CS(C)=O.O>[CH:30]([NH:29][C:2]1[N:7]=[C:6]2[CH:8]=[N:9][CH:10]=[CH:11][C:5]2=[N:4][C:3]=1[N:12]1[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]1)([CH3:32])[CH3:31]

Participants

7

Reactant 4

HCID 6363IsopropylamineHCID 81531DiisopropylethylamineHCID 522689Potassium FluorideHCID 118159282HCID 118159282, compound

Product 1

HCID 118159138HCID 118159138, compoundYield 59%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
23 °C

Procedure

To a flask charged with tert-butyl 4-(3-chloropyrido[3,4-b]pyrazin-2-yl)piperazine-1-carboxylate (3.35 g, 9.58 mmol) and potassium fluoride (0.723 g, 12.45 mmol) in DMSO (25 mL) was added DIPEA (3.34 mL, 19.15 mmol) and propan-2-amine (2.468 mL, 28.7 mmol) at 23° C. The reaction was stirred at 23° C. for 22 hr and diluted with water (100 mL) to furnish an orange, oily sludge. The mixture was cooled to 0° C. to furnish a yellow-orange suspension. The resulting solid was filtered, rinsed with water, and dried in vacuo. The crude material was dissolved in EtOAc, adsorbed on NH silica gel (11 g), and purified via medium pressure chromatography using a gradient of 10% to 100% EtOAc in heptane on an NH 60 μM size 400 column (Shoko Scientific Purif-Pack™) to give the title compound (2.105 g, 59.0%) as a light yellow solid. 1H NMR (500 MHz, DMSO-d6) δ ppm 1.26 (d, J=6.8 Hz, 6H), 1.43 (s, 9H), 3.30-3.33 (m, 4H), 3.52-3.60 (m, 4H), 4.32-4.42 (m, 1H), 6.54 (d, J=7.8 Hz, 1H), 7.43-7.46 (m, 1H), 8.29 (d, J=5.4 Hz, 1H), 8.78 (s, 1H); ESI-MS m/z [M+F]+ 373.0.

Workup

  1. customto furnish an orange, oily sludge
  2. temperatureThe mixture was cooled to 0° C.
  3. customto furnish a yellow-orange suspension
  4. filtrationThe resulting solid was filtered
  5. washrinsed with water
  6. customdried in vacuo
  7. dissolutionThe crude material was dissolved in EtOAc
  8. custompurified via medium pressure chromatography

Sources & evidence

ORD record
ord-c16fda6ed0124023b30706ee3fea3312
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

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