Water → HCID 89781939, compound

HRID 1056094Notes

Reaction equation

HRID 1056094 reaction equation
C([O:3][C:4]([C:6]1[CH:7]=[CH:8][CH:9]=[C:10]2[C:15]=1[N:14]=[C:13]([S:16][CH3:17])[N:12]([CH3:18])[C:11]2=[O:19])=[CH2:5])C.O.C1C(=O)N([Br:28])C(=O)C1>C1COCC1>[Br:28][CH2:3][C:4]([C:6]1[CH:7]=[CH:8][CH:9]=[C:10]2[C:15]=1[N:14]=[C:13]([S:16][CH3:17])[N:12]([CH3:18])[C:11]2=[O:19])=[O:5]

Participants

5

Reactant 3

HCID 962WaterHCID 67184N-bromobutanimideHCID 89782130HCID 89782130, compound

Product 1

HCID 89781939HCID 89781939, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

Et3N (0.094 mL, 0.674 mmol) and TBSOTf (0.131 mL, 0.570 mmol) were sequentially added to a yellow solution of 8-acetyl-3-methyl-2-(methylthio)quinazolin-4(3H)-one (128.7 mg, 0.518 mmol) in DCM (2.7 mL) at 0° C., and the resulting light-yellow solution was stirred at 0° C. for 30 min. The mixture was partitioned between DCM (50 mL) and saturated aq. NaHCO3 (20 mL). The organic layer was separated, and the aq. layer was extracted with DCM (30 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo to provide crude 8-(1-((tert-butyldimethylsilyl)oxy)vinyl)-3-methyl-2-(methylthio)quinazolin-4(3H)-one as a peach-colored solid. This material was combined with 8-(1-ethoxyvinyl)-3-methyl-2-(methylthio)quinazolin-4(3H)-one (35.5 mg, 0.128 mmol), and the resulting mixture was taken up in THF (2.70 mL). Water (0.149 mL, 8.29 mmol) and NBS (115 mg, 0.648 mmol) were sequentially added at 25° C., and the resulting solution was stirred at 25° C. for 30 min. The mixture was partitioned between Et2O (50 mL) and water (30 mL). The organic layer was separated, sequentially washed with saturated aq. NaHCO3 (20 mL), water (20 mL), and brine (20 mL), then dried over Na2SO4, filtered, and concentrated in vacuo to provide crude 8-(2-bromoacetyl)-3-methyl-2-(methylthio)quinazolin-4(3H)-one as an off-white solid. NH4OAc (200 mg, 2.59 mmol) and piperidine-2,4-dione (88 mg, 0.777 mmol) were added to this solid, and the resulting mixture was taken up in EtOH (2.70 mL) and heated under argon in a sealed flask at 40° C. for 16 h. The reaction suspension was vacuum filtered, and the collected solid was washed with MeOH (20 mL) and dried in vacuo. The residue was triturated with DMSO (2.0 mL), and the resulting suspension was vacuum filtered. The collected solid was sequentially washed with MeOH (5 mL) and DCM (5 mL) and dried in vacuo to provide 3-methyl-2-(methylthio)-8-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)quinazolin-4(3H)-one (57.1 mg, 0.168 mmol, 26% yield) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 11.67 (1H, br. s.), 8.05 (1H, dd, J=7.6, 1.2 Hz), 7.95 (1H, dd, J=7.8, 1.0 Hz), 7.44 (1H, t, J=7.8 Hz), 7.03 (1H, d, J=2.3 Hz), 6.96 (1H, br. s.), 3.56 (3H, s), 3.41 (2H, td, J=6.8, 2.2 Hz), 2.85 (2H, t, J=6.9 Hz), 2.74 (3H, s). m/z (ESI, +ve) 341.1 (M+H)+.

Workup

  1. customThe mixture was partitioned between Et2O (50 mL) and water (30 mL)
  2. customThe organic layer was separated
  3. washsequentially washed with saturated aq. NaHCO3 (20 mL), water (20 mL), and brine (20 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8e9d604e5d964fda8decc60a60c41134
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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