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

HRID 1044722
ノート
印刷プレビュー

反応式

HRID 1044722 の反応式
[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]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

9

反応物 6

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

生成物 1

HCID 136162618
6-(5-((2-(methylsulfonyl)ethylamino)methyl)furan-2-yl)quinazolin-4(3H)-one

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
35 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-06da2ceb409b4971996653e9cae9d2cc
出典データセット
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08563719B2

反応ノート

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