Acetic Acid → 6-(5-((2-(methylsulfonyl)ethylamino)methyl)furan-2-yl)quinazolin-4(3H)-one

HRID 1044722Notes

Reaction equation

HRID 1044722 reaction equation
[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]3[O:16][C:15]([CH:17]=O)=[CH:14][CH:13]=3)[CH:10]=2)[N:5]=[CH:4][NH:3]1.Cl.[CH3:20][S:21]([CH2:24][CH2:25][NH2:26])(=[O:23])=[O:22].C(O)(=O)C.CCN(C(C)C)C(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>C1COCC1.O>[CH3:20][S:21]([CH2:24][CH2:25][NH:26][CH2:17][C:15]1[O:16][C:12]([C:9]2[CH:10]=[C:11]3[C:6](=[CH:7][CH:8]=2)[N:5]=[CH:4][NH:3][C:2]3=[O:1])=[CH:13][CH:14]=1)(=[O:23])=[O:22]

Participants

9

Reactant 6

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 17749886Ethanamine, 2-(methylsulfonyl)-, hydrochloride (1:1)HCID 1361626165-(4-Hydroxy-6-quinazolinyl)furan-2-carbaldehyde

Product 1

HCID 1361626186-(5-((2-(methylsulfonyl)ethylamino)methyl)furan-2-yl)quinazolin-4(3H)-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
35 °C

Procedure

To a suspension of the compound of formula (IX) (5 g, 21 mmol) and 2-(methylsulfonyl)ethanamine hydrochloride (4.1 g, 33 mmol) in THF (150 mL) was added acetic acid (5 g, 83 mmol) followed by DIPEA (10.5 g, 83 mmol). The mixture was stirred at 35° C. (internal temperature) for 2.5 h and was then cooled to 20° C. (internal temperature). Sodium tri-acetoxyborohydride (8.8 g, 42 mmol) was added and the mixture was stirred at ambient temperature the reaction was complete (TLC analysis). 25% Aqueous sodium hydroxide (10 mL) and water (50 mL) were added and the mixture was stirred for 30 min The liquid phases were separated and the aqueous layer was extracted with THF (50 mL). The extract was combined with the former organic layer and the mixture was washed with saturated aqueous NH4Cl (50 mL). The organic layer was concentrated under vacuum. The crude product was purified by column chromatography, eluting with 5% MeOH in DCM providing the compound of formula (XI) (3.1 g) after evaporation of the product containing fractions. The compound of formula (XI): 1H NMR (300 MHz, d6-DMSO): δ 2.94 (dt, J=13.8 Hz, J=7.05 Hz, 1H), 3.00 (s, 1H), 3.24 (t, J=6.75 Hz, 1H), 3.77 (s, 1H), 6.42 (d, J=3.3 Hz, 1H), 7.03 (d, J=3.0 Hz, 1H), 7.68 (d, J=8.4 Hz, 1H), 8.06 (s, 1H), 8.09 (dd, J=8.55 Hz, J=2.25 Hz, 1H), 8.31 (d, J=2.1 Hz, 1H).

Workup

  1. temperaturewas then cooled to 20° C. (internal temperature)
  2. stirringthe mixture was stirred at ambient temperature the reaction
  3. stirringthe mixture was stirred for 30 min The liquid phases
  4. customwere separated
  5. extractionthe aqueous layer was extracted with THF (50 mL)
  6. washthe mixture was washed with saturated aqueous NH4Cl (50 mL)
  7. concentrationThe organic layer was concentrated under vacuum
  8. customThe crude product was purified by column chromatography
  9. washeluting with 5% MeOH in DCM providing the compound of formula (XI) (3.1 g)
  10. customafter evaporation of the product
  11. additioncontaining fractions

Sources & evidence

ORD record
ord-06da2ceb409b4971996653e9cae9d2cc
Source dataset
uspto-grants-2013_10
Patent number
US08563719B2

Reaction notes

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