Potassium Phosphate, Tribasic → HCID 89785207, compound

HRID 1056437Notes

Reaction equation

HRID 1056437 reaction equation
Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([NH:12][C:13]([CH3:16])([CH3:15])[CH3:14])[N:8]([CH2:17][CH2:18][S:19]([CH3:22])(=[O:21])=[O:20])[C:7]2=[O:23].[CH3:24][C@@H:25]1[C:29]2[NH:30][C:31](B3OC(C)(C)C(C)(C)O3)=[CH:32][C:28]=2[C:27](=[O:42])[NH:26]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+].O>[C:13]([NH:12][C:9]1[N:8]([CH2:17][CH2:18][S:19]([CH3:22])(=[O:21])=[O:20])[C:7](=[O:23])[C:6]2[C:11](=[C:2]([C:31]3[NH:30][C:29]4[C@@H:25]([CH3:24])[NH:26][C:27](=[O:42])[C:28]=4[CH:32]=3)[CH:3]=[CH:4][CH:5]=2)[N:10]=1)([CH3:16])([CH3:15])[CH3:14]

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 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 89782287HCID 89782287, compound

Product 1

HCID 89785207HCID 89785207, compoundYield 72%

Reagents, catalysts & solvents 3

HCID 54751079XPhos PalladacycleCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
45 °C

Procedure

A glass microwave reaction vessel was charged with 8-bromo-2-(tert-butylamino)-3-(2-(methylsulfonyl)ethyl)quinazolin-4(3H)-one (516c; 88 mg, 0.219 mmol) and (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) (86 mg, 0.262 mmol) in 1,4-dioxane (1.0 mL)/water (0.2 mL) followed by potassium phosphate (0.054 mL, 0.656 mmol) and XPhos precatalyst II (8.6 mg, 10.94 μmol, Sigma Aldrich). The reaction mixture was stirred and heated in an oil bath at 45° C. for 6 h, then cooled to RT. The mixture was diluted with water (25 mL) and the suspension was filtered and the solid was further purified with silica gel chromatography (eluted with 0-4% MeOH in DCM) to give (R)-2-(tert-butylamino)-8-(6-methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrol-2-yl)-3-(2-(methylsulfonyl)ethyl)quinazolin-4(3H)-one (72 mg, 0.157 mmol, 72% yield) as a light yellow solid. MS (ESI, pos. ion) m/z: 458 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 11.86 (1H, s), 7.89 (2H, d, J=7.8 Hz), 7.61 (1H, s), 7.20 (1H, t, J=7.7 Hz), 6.71 (1H, d, J=1.4 Hz), 6.09 (1H, s), 4.47-4.62 (3H, m), 3.56 (2H, t, J=6.7 Hz), 3.12 (3H, s), 1.49 (9H, s), 1.37 (3H, d, J=6.7 Hz).

Workup

  1. customA glass microwave reaction vessel
  2. temperaturecooled to RT
  3. filtrationthe suspension was filtered
  4. customthe solid was further purified with silica gel chromatography (eluted with 0-4% MeOH in DCM)

Sources & evidence

ORD record
ord-151ddc22e5bc4eaea8d8bf788047fd8b
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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