Toluene → 2-(4-cyclopropylmethylphenyl)-N-isobutoxycarbonyl-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide

HRID 361473노트

반응식

HRID 361473 반응식
[CH:1]1([CH2:4][C:5]2[CH:10]=[CH:9][C:8](B(O)O)=[CH:7][CH:6]=2)[CH2:3][CH2:2]1.Cl[C:15]1[C:20]([S:21]([N:24]([C:34]([O:36][CH2:37][CH:38]([CH3:40])[CH3:39])=[O:35])[C:25]2[C:30]([O:31][CH3:32])=[N:29][C:28]([CH3:33])=[CH:27][N:26]=2)(=[O:23])=[O:22])=[CH:19][CH:18]=[CH:17][N:16]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>O.C(O)C>[CH:1]1([CH2:4][C:5]2[CH:10]=[CH:9][C:8]([C:15]3[C:20]([S:21]([N:24]([C:34]([O:36][CH2:37][CH:38]([CH3:40])[CH3:39])=[O:35])[C:25]4[C:30]([O:31][CH3:32])=[N:29][C:28]([CH3:33])=[CH:27][N:26]=4)(=[O:22])=[O:23])=[CH:19][CH:18]=[CH:17][N:16]=3)=[CH:7][CH:6]=2)[CH2:3][CH2:2]1

참가 물질

7

반응물 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 11015197Isobutyl (2-chloropyridin-3-yl)sulfonyl(3-methoxy-5-methylpyrazin-2-yl)carbamateHCID 18754990[4-(Cyclopropylmethyl)phenyl]boronic acid

생성물 1

HCID 211863262-(4-cyclopropylmethylphenyl)-N-isobutoxycarbonyl-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide수율 50.3%

시약·촉매·용매 2

HCID 702Ethanol용매HCID 962Water용매

반응 조건

온도
80 °C

실험 절차

4-(cyclopropylmethyl)benzeneboronic acid (1.5 g), 2-chloro-N-isobutoxycarbonyl-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide (2.99 g) and sodium carbonate (912 mg) were added to a mixture of toluene (66 ml), ethanol (33 ml) and water (24 ml). The mixture was deoxygenated by alternatively bubbling argon through and evacuating (3 cycles) and tetrakis(triphenylphosphine) palladium(0) (347 mgs) was added. The reaction mixture was heated to 80° C. for 18 hours with efficient stirring and, after cooling, ethyl acetate (50 ml) and water (30 ml) were added. The organic phase was separated and the aqueous layer exracted with ethyl acetate (2×30 ml). The combined organic phases were washed with brine (15 ml), dried (MgSO4) and evaporated. The residue was purified by chromatography on a Mega Bond Elut column, eluting with a gradient of ethyl acetate in hexane (0-100%) to give 2-(4-cyclopropylmethylphenyl)-N-isobutoxycarbonyl-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide (1.85 g); 1H NMR (d6 -DMSO): 0.25 (q, 2 H), 0.54 (m, 2 H), 1.03 (M, 1 H), 1.64 (m, 1 H), 2.55 (s, 3 H), 2.60 (d, 2 H), 3.83 (d, 2 H), 3.98 (s, 3 H), 7.33 (d, 2 H), 7.46 (d, 2 H), 7.77 (dd, 1 H), 8.15 (s, 1 H), 8.10-8.95 (m, 2 H); mass spectrum (+ve ESP) 511 (M+H)+.

후처리

  1. customThe mixture was deoxygenated by alternatively bubbling argon through and
  2. customevacuating (3 cycles) and tetrakis(triphenylphosphine) palladium(0) (347 mgs)
  3. additionwas added
  4. temperatureafter cooling
  5. additionethyl acetate (50 ml) and water (30 ml) were added
  6. customThe organic phase was separated
  7. washThe combined organic phases were washed with brine (15 ml)
  8. dry with materialdried (MgSO4)
  9. customevaporated
  10. customThe residue was purified by chromatography on a Mega Bond Elut column
  11. washeluting with a gradient of ethyl acetate in hexane (0-100%)

출처 및 근거

ORD 기록
ord-ce599ac7c7884eac8709da3b6ce6005b
출처 데이터셋
uspto-grants-1999_02
특허 번호
US05866568

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