Sodium Carbonate → tert-butyl N-[[4-[5-[3-amino-6-[2-(1-cyano-1-methyl-ethyl)-4-pyridyl]pyrazin-2-yl]-1,3,4-oxadiazol-2-yl]phenyl]methyl]-N-methyl-carbamate

HRID 331511Notes

Reaction equation

HRID 331511 reaction equation
[CH3:1][C:2]([C:6]1[CH:11]=[C:10](B2OC(C)(C)C(C)(C)O2)[CH:9]=[CH:8][N:7]=1)([CH3:5])[C:3]#[N:4].[NH2:21][C:22]1[C:23]([C:29]2[O:33][C:32]([C:34]3[CH:39]=[CH:38][C:37]([CH2:40][N:41]([CH3:49])[C:42](=[O:48])[O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[CH:36][CH:35]=3)=[N:31][N:30]=2)=[N:24][C:25](Br)=[CH:26][N:27]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.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>[NH2:21][C:22]1[C:23]([C:29]2[O:33][C:32]([C:34]3[CH:35]=[CH:36][C:37]([CH2:40][N:41]([CH3:49])[C:42](=[O:48])[O:43][C:44]([CH3:45])([CH3:46])[CH3:47])=[CH:38][CH:39]=3)=[N:31][N:30]=2)=[N:24][C:25]([C:10]2[CH:9]=[CH:8][N:7]=[C:6]([C:2]([C:3]#[N:4])([CH3:1])[CH3:5])[CH:11]=2)=[CH:26][N:27]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 59472114HCID 59472114, compoundHCID 70819311HCID 70819311, compound

Product 1

HCID 70819550tert-butyl N-[[4-[5-[3-amino-6-[2-(1-cyano-1-methyl-ethyl)-4-pyridyl]pyrazin-2-yl]-1,3,4-oxadiazol-2-yl]phenyl]methyl]-N-methyl-carbamateYield 100%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 2-methyl-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]propane nitrile (103 mg, 0.3784 mmol) in dioxane (1.133 mL) was added of tert-butyl N-[[4-[5-(3-amino-6-bromo-pyrazin-2-yl)-1,3,4-oxadiazol-2-yl]phenyl]methyl]-N-methyl-carbamate (174.6 mg, 0.3784 mmol) and reaction was treated with 2 M aqueous solution of sodium carbonate (567.5 μL of 2 M, 1.135 mmol). The reaction mixture was degassed with 5× vacuum/nitrogen cycles. Then Pd(PPh3)4 (43.85 mg, 0.03795 mmol) was added to the reaction mixture. The reaction mixture was degassed further with 5× vacuum/nitrogen cycles and the reaction mixture was stirred in a microwave at 150° C. for 30 minutes. The reaction was diluted with ethyl acetate and aqueous sodium bicarbonate solution. The organic extracts were separated and washed with brine (×1), dried over MgSO4, filtered and concentrated in vacuo to give a black oil. Taken onto the next step without further purification (199.3 mg, assumed 100% yield).

Workup

  1. customThe reaction mixture was degassed with 5× vacuum/nitrogen cycles
  2. customThe reaction mixture was degassed further with 5× vacuum/nitrogen cycles
  3. additionThe reaction was diluted with ethyl acetate and aqueous sodium bicarbonate solution
  4. customThe organic extracts were separated
  5. washwashed with brine (×1)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a black oil
  10. customTaken onto the next step without further purification (199.3 mg, assumed 100% yield)

Sources & evidence

ORD record
ord-64c47f74fa584877b548928bd630c908
Source dataset
uspto-grants-2014_11
Patent number
US08877759B2

Reaction notes

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