Potassium Carbonate → HCID 118364856, compound

HRID 1478579Notes

Reaction equation

HRID 1478579 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]=[C:26]([CH:29]=[CH:30][CH:31]=5)[C:27]#[N:28])=[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:44]1[CH2:49][CH2:48][CH2:47][CH2:46][CH:45]1[O:50][CH2:51][CH2:52][N:53]1[CH:57]=[C:56](B2OC(C)(C)C(C)(C)O2)[CH:55]=[N:54]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>[O:44]1[CH2:49][CH2:48][CH2:47][CH2:46][CH:45]1[O:50][CH2:51][CH2:52][N:53]1[CH:57]=[C:56]([C:2]2[CH:3]=[N:4][C:5]([N:8]3[CH2:13][CH2:12][O:11][C@H:10]([CH2:14][N:15]4[C:19]5=[N:20][C:21]([C:24]6[CH:25]=[C:26]([CH:29]=[CH:30][CH:31]=6)[C:27]#[N:28])=[CH:22][N:23]=[C:18]5[N:17]=[N:16]4)[CH2:9]3)=[N:6][CH:7]=2)[CH:55]=[N:54]1

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 118364736HCID 118364736, compound

Product 1

HCID 118364856HCID 118364856, compoundYield 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)-3-(1-((4-(5-bromopyrimidin-2-yl)morpholine-2-yl)methyl)-1H-[1,2,3]-triazolo[4,5-b]pyrazin-6-yl)benzonitrile 50 mg (0.10 mmol) was added, and then potassium carbonate 43 mg (0.31 mmol) was added. Pd(dppf)2Cl2 4 mg (0.005 mmol) was further added, 1,4-dioxane 2 ml and 1-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)-1H-pyrazole 40 mg (0.13 mmol) were added, and then H2O 0.5 ml was added. 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% ethyl acetate/hexane gave 3-(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 48 mg (0.08 mmol) with a yield of 70%.

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-f6b0a978f76640d0836232d2513eed85
Source dataset
uspto-grants-2016_08
Patent number
US09403831B2

Reaction notes

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