Sodium Carbonate → (S)-2-fluoro-5-(1-((4-(5-(3-fluoro-4-formylphenyl)pyrimidin-2-yl)morpholin-2-yl)methyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl)benzonitrile

HRID 1478586Notes

Reaction equation

HRID 1478586 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.[Na+].[Na+].[F:39][C:40]1[CH:47]=[C:46](B2OC(C)(C)C(C)(C)O2)[CH:45]=[CH:44][C:41]=1[CH:42]=[O:43]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[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:46]6[CH:45]=[CH:44][C:41]([CH:42]=[O:43])=[C:40]([F:39])[CH:47]=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

6

Reactant 3

HCID 10340Sodium CarbonateHCID 532171132-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehydeHCID 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 118364737(S)-2-fluoro-5-(1-((4-(5-(3-fluoro-4-formylphenyl)pyrimidin-2-yl)morpholin-2-yl)methyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl)benzonitrileYield 91%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

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 1M Na2CO3 (0.31 mL, 0.31 mmol) was added. Pd(PPh3)4 (6 mg, 0.005 mmol) was further added, and 1,4-dioxane (1 mL) and 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)benzaldehyde (38 mg, 0.15 mmol) were added. The mixture was stirred at room temperature for 10 minutes under nitrogen gas, and then stirred at 105° C. for 3 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. Solid was generated using ether and hexane, followed by filtration, to give (S)-2-fluoro-5-(1-((4-(5-(3-fluoro-4-formylphenyl)pyrimidin-2-yl)morpholin-2-yl)methyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl)benzonitrile (49 mg, 0.091 mmol) with a yield of 90%.

Workup

  1. stirringstirred at 105° C. for 3 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
  5. filtrationfollowed by filtration

Sources & evidence

ORD record
ord-2d08150c9a714f71a028682a87db8bdb
Source dataset
uspto-grants-2016_08
Patent number
US09403831B2

Reaction notes

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