Potassium Carbonate → HCID 89783636, compound

HRID 1056367Notes

Reaction equation

HRID 1056367 reaction equation
C(=O)([O-])[O-].[K+].[K+].[CH3:7][C@@H:8]1[C:12]2[NH:13][C:14](B3OC(C)(C)C(C)(C)O3)=[CH:15][C:11]=2[C:10](=[O:25])[NH:9]1.Br[C:27]1[CH:28]=[CH:29][CH:30]=[C:31]2[C:36]=1[N:35]=[C:34]([NH:37][C:38]([CH3:41])([CH3:40])[CH3:39])[N:33]([C:42]1[CH:43]=[N:44][CH:45]=[CH:46][CH:47]=1)[C:32]2=[O:48]>>[C:38]([NH:37][C:34]1[N:33]([C:42]2[CH:43]=[N:44][CH:45]=[CH:46][CH:47]=2)[C:32](=[O:48])[C:31]2[C:36](=[C:27]([C:14]3[NH:13][C:12]4[C@@H:8]([CH3:7])[NH:9][C:10](=[O:25])[C:11]=4[CH:15]=3)[CH:28]=[CH:29][CH:30]=2)[N:35]=1)([CH3:41])([CH3:39])[CH3:40]

Participants

4

Reactant 3

HCID 11430Potassium CarbonateHCID 89781988(R)-6-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-oneHCID 89782061HCID 89782061, compound

Product 1

HCID 89783636HCID 89783636, compoundYield 73.1%

Conditions

Temperature
80 °C

Procedure

Argon was bubbled into a slurry of potassium carbonate (Mallinkrodt; 0.074 g, 0.536 mmol), dichlorobis(p-dimethylaminophenylditbutylphosphine)palladium(ii) (Aldrich; 4.74 mg, 6.70 μmol), (R)-6-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (705; 0.070 g, 0.268 mmol), 8-bromo-2-(tert-butylamino)-3-(pyridin-3-yl)quinazolin-4(3H)-one (404a; 0.050 g, 0.134 mmol) for 1 min. The reaction was sealed and heated to 80° C. for 30 min. The reaction was adsorbed onto 0.7 g silica gel and dried in vacuo. The material was treated with purified by silica gel chromatography (12 g column) using 0-100% (90/10 DCM/MeOH) in DCM. The product-containing fractions were concentrated to afford (R)-2-(tert-butylamino)-8-(6-methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrol-2-yl)-3-(pyridin-3-yl)quinazolin-4(3H)-one (0.042 g, 0.098 mmol, 73% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.91 (1H, s), 8.74 (1H, dd, J=4.9, 1.6 Hz), 8.64 (1H, d, J=2.2 Hz), 7.91-7.99 (2H, m), 7.89 (1H, dd, J=7.8, 1.6 Hz), 7.59-7.69 (2H, m), 7.24 (1H, t, J=7.6 Hz), 6.77 (1H, d, J=1.6 Hz), 4.61 (1H, s), 4.49-4.58 (1H, m), 1.31-1.41 (12H, m). m/z (ESI, +ve ion) 429.0 (M+H)+.

Workup

  1. customThe reaction was sealed
  2. customdried in vacuo
  3. additionThe material was treated
  4. customwith purified by silica gel chromatography (12 g column)
  5. concentrationThe product-containing fractions were concentrated

Sources & evidence

ORD record
ord-a9640d8011ba4882813405c0a52fe75f
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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