Tetrabutylammonium Fluoride → (R)-2-(tert-butylamino)-3-(3-hydroxypropyl)-8-(6-methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrol-2-yl)quinazolin-4(3H)-one

HRID 1056389Notes

Reaction equation

HRID 1056389 reaction equation
[C:1]([NH:5][C:6]1[N:15]([CH2:16][CH2:17][CH2:18][O:19][Si](C(C)(C)C)(C)C)[C:14](=[O:27])[C:13]2[C:8](=[C:9]([C:28]3[NH:32][C:31]4[C@@H:33]([CH3:37])[NH:34][C:35](=[O:36])[C:30]=4[CH:29]=3)[CH:10]=[CH:11][CH:12]=2)[N:7]=1)([CH3:4])([CH3:3])[CH3:2].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[C:1]([NH:5][C:6]1[N:15]([CH2:16][CH2:17][CH2:18][OH:19])[C:14](=[O:27])[C:13]2[C:8](=[C:9]([C:28]3[NH:32][C:31]4[C@@H:33]([CH3:37])[NH:34][C:35](=[O:36])[C:30]=4[CH:29]=3)[CH:10]=[CH:11][CH:12]=2)[N:7]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 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)-one

Product 1

HCID 89783577(R)-2-(tert-butylamino)-3-(3-hydroxypropyl)-8-(6-methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrol-2-yl)quinazolin-4(3H)-oneYield 90%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a slurry of (R)-2-(tert-butylamino)-3-(3-((tert-butyldimethylsilyl)oxy)propyl)-8-(6-methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrolo-2-yl)quinazolin-4(3H)-one (500c; 0.047 g, 0.090 mmol) in 0.7 mL THF was added TBAF 1.0 M in THF (0.18 mL, 0.179 mmol). The reaction became a yellow solution. After 30 min, the reaction was adsorbed onto 0.7 g silica gel and 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)-3-(3-hydroxypropyl)-8-(6-methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrol-2-yl)quinazolin-4(3H)-one (0.033 g, 0.081 mmol, 90% yield) as a white solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 11.91 (1H, br. s.), 7.88 (2H, d, J=7.8 Hz), 7.61 (1H, s), 7.17 (1H, t, J=7.7 Hz), 6.70 (1H, s), 6.61 (1H, s), 5.31 (1H, br. s.), 4.53 (1H, q, J=6.6 Hz), 4.09 (2H, t, J=6.3 Hz), 3.47 (2H, t, J=5.5 Hz), 1.83 (2H, quin, J=5.9 Hz), 1.49 (9H, s), 1.37 (3H, d, J=6.7 Hz). m/z (ESI, +ve ion) 410.1 (M+H)+.

Workup

  1. custompurified by silica gel chromatography (12 g column)
  2. concentrationThe product-containing fractions were concentrated

Sources & evidence

ORD record
ord-80fdddc1ec124e84acfdbc113c6ddf22
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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