Potassium Carbonate → (R)-2-(tert-butylamino)-3-(3-((tert-butyldimethylsilyl)oxy)propyl)-8-(6-methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrol-2-yl)quinazolin-4(3H)-one

HRID 1056388Notes

Reaction equation

HRID 1056388 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]([CH2:42][CH2:43][CH2:44][O:45][Si:46]([C:49]([CH3:52])([CH3:51])[CH3:50])([CH3:48])[CH3:47])[C:32]2=[O:53]>O1CCOCC1.O.C(C1C(C(C)(C)C)=C([Pd]Cl)C=CC=1NC)(C)(C)C>[C:38]([NH:37][C:34]1[N:33]([CH2:42][CH2:43][CH2:44][O:45][Si:46]([C:49]([CH3:52])([CH3:51])[CH3:50])([CH3:47])[CH3:48])[C:32](=[O:53])[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)([CH3:39])([CH3:41])[CH3:40]

Participants

7

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 897852468-bromo-2-(tert-butylamino)-3-(3-((tert-butyldimethylsilyl)oxy)propyl)quinazolin-4(3H)-one

Product 1

HCID 89783734(R)-2-(tert-butylamino)-3-(3-((tert-butyldimethylsilyl)oxy)propyl)-8-(6-methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrol-2-yl)quinazolin-4(3H)-oneYield 54.9%

Reagents, catalysts & solvents 3

HCID 178482226HCID 178482226, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Potassium carbonate (Mallinkrodt; 0.091 g, 0.657 mmol), 1,1-bis[(di-t-butyl-p-methylaminophenyl]palladium(ii) chloride (Aldrich; 5.82 mg, 8.22 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; 0.086 g, 0.329 mmol), 8-bromo-2-(tert-butylamino)-3-(3-((tert-butyldimethylsilyl)oxy)propyl)quinazolin-4(3H)-one (500b; 0.077 g, 0.164 mmol) were combined in 2 mL dioxane and 0.4 mL water. Argon was bubbled into the reaction for 1 min. The reaction was sealed and heated to 80° C. for 1 h. The reaction was adsorbed onto 1 g silica gel and The material was and purified by silica gel chromatography (12 g column) using 0-100% EtOAc/hexanes. The product-containing fractions were concentrated to afford (R)-2-(tert-butylamino)-3-(3-((tert-butyldimethylsilyl)oxy)propyl)-8-(6-methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrol-2-yl)quinazolin-4(3H)-one (0.047 g, 0.090 mmol, 54.6% yield) as a light-yellow solid: 1H NMR (400 MHz, CDCl3) δ ppm 12.52 (1H, br. s.), 7.88-8.23 (2H, m), 7.22 (1H, t, J=7.7 Hz), 6.84 (1H, d, J=1.2 Hz), 5.89 (1H, br. s.), 5.31 (1H, s), 4.68 (1H, q, J=6.7 Hz), 4.18 (2H, t, J=7.1 Hz), 3.79 (2H, t, J=5.3 Hz), 1.92-2.02 (2H, m), 1.65 (9H, s), 1.54 (3H, d, J=6.8 Hz), 0.96 (9H, s), 0.15 (6H, s). m/z (ESI, +ve ion) 524.2 (M+H)+.

Workup

  1. customArgon was bubbled into the reaction for 1 min
  2. customThe reaction was sealed
  3. custompurified by silica gel chromatography (12 g column)
  4. concentrationThe product-containing fractions were concentrated

Sources & evidence

ORD record
ord-d8dc0a49e4284f82b6fbf0ff9921f1fb
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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