Sodium Carbonate → (S)-tert-butyl 1-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-ylcarbamoyl)-3-phenyl-5,6-dihydroimidazo[1,5-a]pyrazine-7(8H)-carboxylate

HRID 2110189Notes

Reaction equation

HRID 2110189 reaction equation
Br[C:2]1[N:6]2[CH2:7][CH2:8][N:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:10][C:5]2=[C:4]([C:18](=[O:29])[NH:19][C@@H:20]([C:25]([CH3:28])([CH3:27])[CH3:26])[C:21]([NH:23][CH3:24])=[O:22])[N:3]=1.[C:30]1(B(O)O)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:26][C:25]([CH3:28])([CH3:27])[C@H:20]([NH:19][C:18]([C:4]1[N:3]=[C:2]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[N:6]2[CH2:7][CH2:8][N:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:10][C:5]=12)=[O:29])[C:21]([NH:23][CH3:24])=[O:22]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 57635359(S)-tert-butyl 3-bromo-1-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-ylcarbamoyl)-5,6-dihydroimidazo[1,5-a]pyrazine-7(8H)-carboxylate

Product 1

HCID 25132454(S)-tert-butyl 1-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-ylcarbamoyl)-3-phenyl-5,6-dihydroimidazo[1,5-a]pyrazine-7(8H)-carboxylateYield 76.1%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

Intermediate 1J (0.20 g, 0.42 mmol) was dissolved in dioxane (4 mL) and phenylboronic acid (0.10 g, 0.85 mmol) was added, followed by 2N Na2CO3 solution (0.70 mL, 1.39 mmol). The resulting mixture was degassed with nitrogen and tetrakis(triphenylphosphine) palladium(0) (0.073 g, 0.06 mmol) was added. The mixture was heated in a microwave reactor at 150° C. for 20 min. The reaction mixture was filtered through a celite pad, rinsed with methanol and the combined filtrate and washings were concentrated. The residue was purified by normal phase chromatography, eluting with 0-100% hexanes/ethyl acetate to provide Compound 1 as a yellow solid (0.15 g, 75%).

Workup

  1. additionwas added
  2. filtrationThe reaction mixture was filtered through a celite pad
  3. washrinsed with methanol
  4. concentrationthe combined filtrate and washings were concentrated
  5. customThe residue was purified by normal phase chromatography
  6. washeluting with 0-100% hexanes/ethyl acetate

Sources & evidence

ORD record
ord-164f2d9110c7434d9180bdd5ecd92b8d
Source dataset
uspto-grants-2009_04
Patent number
US07517874B2

Reaction notes

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