Potassium Carbonate → 2-fluoro-5-(1-(((2S)-4-(5-(1-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)-1H-pyrazol-4-yl)pyrimidin-2-yl)morpholine-2-yl)-methyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl)benzonitrile

HRID 1478580Notes

Reaction equation

HRID 1478580 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.[O:45]1[CH2:50][CH2:49][CH2:48][CH2:47][CH:46]1[O:51][CH2:52][CH2:53][N:54]1[CH:58]=[C:57](B2OC(C)(C)C(C)(C)O2)[CH:56]=[N:55]1>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>[F:32][C:27]1[CH:26]=[CH:25][C:24]([C:21]2[N:20]=[C:19]3[N:15]([CH2:14][C@H:10]4[O:11][CH2:12][CH2:13][N:8]([C:5]5[N:4]=[CH:3][C:2]([C:57]6[CH:56]=[N:55][N:54]([CH2:53][CH2:52][O:51][CH:46]7[CH2:47][CH2:48][CH2:49][CH2:50][O:45]7)[CH:58]=6)=[CH:7][N:6]=5)[CH2:9]4)[N:16]=[N:17][C:18]3=[N:23][CH:22]=2)=[CH:31][C:28]=1[C:29]#[N:30]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 593418191-[2-(oxan-2-yloxy)ethyl]-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 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 1183647742-fluoro-5-(1-(((2S)-4-(5-(1-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)-1H-pyrazol-4-yl)pyrimidin-2-yl)morpholine-2-yl)-methyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl)benzonitrileYield 80%

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 50 mg (0.10 mmol) was added, and then potassium carbonate 41 mg (0.30 mmol) was added. Pd(dppf)2Cl2 4 mg (0.005 mmol) was further added, followed by 1,4-dioxane ml, 1-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)-4-(4,4,5,5-tetra methyl-1,3,2-dioxaborolane-2-yl)-1H-pyrazole 38 mg (0.12 mmol) and then 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 60% ethyl acetate/hexane gave 2-fluoro-5-(1-(((2S)-4-(5-(1-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)-1H-pyrazol-4-yl)pyrimidin-2-yl)morpholine-2-yl)-methyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl)benzonitrile 49 mg (0.08 mmol) with a yield of 80%.

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-8981febf39e64026999adf97b9f2c34a
Source dataset
uspto-grants-2016_08
Patent number
US09403831B2

Reaction notes

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