Sulfoxonium, trimethyl-, iodide (1:1) → 8-Bromo-2-(1-phenylcyclopropyl)quinazoline

HRID 1056072Notes

Reaction equation

HRID 1056072 reaction equation
[CH3:1]C(C)([O-])C.[K+].[I-].C[S+](C)(C)=O.[Br:13][C:14]1[CH:15]=[CH:16][CH:17]=[C:18]2[C:23]=1[N:22]=[C:21]([C:24]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[CH2:25])[N:20]=[CH:19]2>CS(C)=O.O.Cl>[Br:13][C:14]1[CH:15]=[CH:16][CH:17]=[C:18]2[C:23]=1[N:22]=[C:21]([C:24]1([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH2:1][CH2:25]1)[N:20]=[CH:19]2

Participants

7

Reactant 3

HCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 23665647Potassium tert-butoxideHCID 897821478-Bromo-2-(1-phenylvinyl)quinazoline

Product 1

HCID 897818618-Bromo-2-(1-phenylcyclopropyl)quinazolineYield 37.4%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 679Dimethyl SulfoxideSolvent2×HCID 962WaterSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of potassium tert-butoxide (284 mg, 2.532 mmol) and trimethylsulfoxonium iodide (Aldrich; 557 mg, 2.532 mmol) in anhydrous DMSO (6.5 mL) was stirred under argon at 25° C. for 10 min. A solution of 8-bromo-2-(1-phenylvinyl)quinazoline (393.9 mg, 1.266 mmol) in DMSO (10.0 mL) was added (dropwise, over 8 min), and the resulting brown solution was stirred at 25° C. for 30 min. The reaction was diluted with water (20 mL) and 1.0N aq. HCl (1.2 mL), then partitioned between DCM (120 mL) and water (70 mL). The aq. layer was extracted with additional DCM (70 mL), and the combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0-40% EtOAc/hexanes) provided 8-bromo-2-(1-phenylcyclopropyl)quinazoline (153.8 mg, 0.473 mmol, 37% yield) as a light-yellow solid: 1H NMR (400 MHz, CDCl3) δ ppm 9.18 (1H, s), 8.11 (1H, d, J=7.4 Hz), 7.78 (1H, d, J=8.0 Hz), 7.50 (2H, d, J=7.6 Hz), 7.38 (3H, td, J=7.6, 2.6 Hz), 7.30 (1H, t, J=7.4 Hz), 1.92-1.98 (2H, m), 1.51-1.55 (2H, m). m/z (ESI, +ve) 325.1 (M+H)+.

Workup

  1. stirringwas stirred at 25° C. for 30 min
  2. custompartitioned between DCM (120 mL) and water (70 mL)
  3. extractionThe aq. layer was extracted with additional DCM (70 mL)
  4. dry with materialthe combined organic extracts were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customChromatographic purification of the residue (silica gel, 0-40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-d399048beac54c2083a0f05bded65a11
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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