Potassium Carbonate → (S)-tert-butyl 4-(2-(2-((6-(3-cyano-4-fluorophenyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)morpholino)pyrimidin-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 1478581Notes

Reaction equation

HRID 1478581 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][O:11][C@H:10]([CH2:14][N:15]3[C:19]4=[N:20][C:21]([C:24]5[CH:25]=[CH:26][C:27]([F:32])=[C:28]([CH:31]=5)[C:29]#[N:30])=[CH:22][N:23]=[C:18]4[N:17]=[N:16]3)[CH2:9]2)=[N:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].O1CCOCC1.CC1(C)C(C)(C)OB([C:53]2[CH2:58][CH2:57][N:56]([C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])[CH2:55][CH:54]=2)O1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[C:29]([C:28]1[CH:31]=[C:24]([C:21]2[N:20]=[C:19]3[N:15]([CH2:14][C@@H:10]4[CH2:9][N:8]([C:5]5[N:4]=[CH:3][C:2]([C:53]6[CH2:58][CH2:57][N:56]([C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])[CH2:55][CH:54]=6)=[CH:7][N:6]=5)[CH2:13][CH2:12][O:11]4)[N:16]=[N:17][C:18]3=[N:23][CH:22]=2)[CH:25]=[CH:26][C:27]=1[F:32])#[N:30]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 118364734(S)-5-(1-((4-(5-bromopyrimidin-2-yl)morpholine-2-yl)methyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl)-2-fluorobenzonitrile

Product 1

HCID 118364783(S)-tert-butyl 4-(2-(2-((6-(3-cyano-4-fluorophenyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)morpholino)pyrimidin-5-yl)-5,6-dihydropyridine-1(2H)-carboxylateYield 87%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Procedure

In a pressure tube reactor, ((S)-5-(1-((4-(5-bromopyrimidin-2-yl)morpholine-2-yl)methyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl)-2-fluorobenzonitrile 100 mg (0.20 mmol) was added, and potassium carbonate 83 mg (0.60 mmol) was added. Pd(dppf)2Cl2 8 mg (0.01 mmol) was further added, followed by 1,4-dioxane 3 ml, tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate 74 mg (0.24 mmol), and H2O 0.5 ml. The mixture was stirred at room temperature for 10 minutes under nitrogen gas, and then stirred at 80° C. for 2 hours. When the reaction was completed, the organic layer was extracted with ethyl acetate and water, and the extra water was removed by sodium sulfate, followed by concentration under reduced pressure. Column chromatography using 50% ethylacetate/hexane gave (S)-tert-butyl 4-(2-(2-((6-(3-cyano-4-fluorophenyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)morpholino)pyrimidin-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate 104 mg (0.17 mmol) with a yield of 87%.

Workup

  1. stirringstirred at 80° C. for 2 hours
  2. extractionthe organic layer was extracted with ethyl acetate and water
  3. customthe extra water was removed by sodium sulfate
  4. concentrationfollowed by concentration under reduced pressure

Sources & evidence

ORD record
ord-8a3e807cc7b34fe2bca9384b86e90907
Source dataset
uspto-grants-2016_08
Patent number
US09403831B2

Reaction notes

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