Potassium Carbonate → (R)-2-(4-amino-2-(tert-butylamino)quinazolin-8-yl)-6-methyl-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one

HRID 1056372Notes

Reaction equation

HRID 1056372 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:32]2[NH2:42]>O1CCOCC1.O>[NH2:42][C:32]1[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]=[C:34]([NH:37][C:38]([CH3:41])([CH3:40])[CH3:39])[N:33]=1

Participants

6

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 897822178-bromo-N2-(tert-butyl)quinazoline-2,4-diamine

Product 1

HCID 89784289(R)-2-(4-amino-2-(tert-butylamino)quinazolin-8-yl)-6-methyl-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-oneYield 49.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Argon was bubbled into a slurry of potassium carbonate (Mallinkrodt; 0.140 g, 1.016 mmol), dichlorobis(p-dimethylaminophenylditbutylphosphine)palladium (ii) (Aldrich; 0.018 g, 0.025 mmol), (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; 0.133 g, 0.51 mmol), 8-bromo-N2-(tert-butyl)quinazoline-2,4-diamine (484b; 0.075 g, 0.254 mmol) in 2 mL dioxane and 0.4 mL water for 1 min. The reaction was sealed and heated to 80° C. for 30 min. The reaction was adsorbed onto 1 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/2.0 M NH3/MeOH) in DCM). The product-containing fractions were concentrated to afford (R)-2-(4-amino-2-(tert-butylamino)quinazolin-8-yl)-6-methyl-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (0.044 g, 0.126 mmol, 49% yield) as an orange solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 13.13 (1H, s), 7.97 (1H, dd, J=7.6, 1.2 Hz), 7.83 (1H, d, J=8.0 Hz), 7.59 (1H, s), 7.32-7.47 (2H, m), 7.02 (1H, t, J=7.7 Hz), 6.76 (1H, d, J=1.2 Hz), 6.47 (1H, br. s.), 4.56 (1H, q, J=6.7 Hz), 1.49 (9H, s), 1.41 (3H, d, J=6.7 Hz). m/z (ESI, +ve ion) 351.0 (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-ac1678d9f0af401e8a9c3b451361f0f7
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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