Sodium Hydroxide → (S)-4-(5-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)pyrimidin-2-yl)-2-((6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)morpholine

HRID 1478568Notes

Reaction equation

HRID 1478568 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[N:12]=[C:11]3[N:13]([CH2:16][C@@H:17]4[CH2:22][N:21]([C:23]5[N:28]=[CH:27][C:26]([C:29]6[CH2:34][CH2:33][N:32]([C:35](OC(C)(C)C)=O)[CH2:31][CH:30]=6)=[CH:25][N:24]=5)[CH2:20][CH2:19][O:18]4)[N:14]=[N:15][C:10]3=[N:9][CH:8]=2)[CH:4]=[N:3]1.[OH-].[Na+]>C=O.C(O)(=O)C>[CH3:35][N:32]1[CH2:31][CH:30]=[C:29]([C:26]2[CH:27]=[N:28][C:23]([N:21]3[CH2:20][CH2:19][O:18][C@H:17]([CH2:16][N:13]4[C:11]5=[N:12][C:7]([C:5]6[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=6)=[CH:8][N:9]=[C:10]5[N:15]=[N:14]4)[CH2:22]3)=[N:24][CH:25]=2)[CH2:34][CH2:33]1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 118364759(S)-tert-butyl 4-(2-(2-((6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)morpholino)pyrimidin-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate

Product 1

HCID 73504290(S)-4-(5-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)pyrimidin-2-yl)-2-((6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)morpholineYield 59.5%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 712FormaldehydeSolvent

Conditions

Temperature
95 °C

Procedure

(S)-tert-butyl 4-(2-(2-((6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)morpholino)pyrimidin-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate (36 mg, 0.06 mmol) was dissolved in 35% HCHO (0.1 ml) and acetic acid (0.5 ml), followed by stirring at 95° C. overnight. After the completion of the reaction, the reaction mixture was adjusted to pH 11-12 with NaOH (aq.), and extracted with H2O and EA, followed by drying (Na2SO4), filtration and concentration under reduced pressure, and the residue was purified by column chromatography (MeOH:MC=1:10), to give (S)-4-(5-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)pyrimidin-2-yl)-2-((6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)morpholine (16.9 mg, 56%).

Workup

  1. customAfter the completion of the reaction
  2. extractionextracted with H2O and EA
  3. customby drying
  4. filtration(Na2SO4), filtration and concentration under reduced pressure
  5. customthe residue was purified by column chromatography (MeOH:MC=1:10)

Sources & evidence

ORD record
ord-e9942982e06b407d8dc662e01ecfeb5d
Source dataset
uspto-grants-2016_08
Patent number
US09403831B2

Reaction notes

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