Sodium Carbonate → tert-butyl 4-(5-methoxy-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 2378978ノート

反応式

HRID 2378978 の反応式
[CH3:1][O:2][C:3]1[N:8]=[C:7]2[CH:9]=[CH:10][N:11]([CH3:12])[C:6]2=[CH:5][C:4]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].[Cl-].[Li+].FC(F)(F)S(O[C:30]1[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH:31]=1)(=O)=O>O.O1CCOCC1>[CH3:1][O:2][C:3]1[N:8]=[C:7]2[CH:9]=[CH:10][N:11]([CH3:12])[C:6]2=[CH:5][C:4]=1[C:30]1[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH:31]=1

参加物

7

反応物 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 10991161Tert-butyl 4-(trifluoromethanesulfonyloxy)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 59006378B-(5-methoxy-1-methyl-1h-pyrrolo[3,2-b]pyridin-6-yl)-boronic acid

生成物 1

HCID 59006345tert-butyl 4-(5-methoxy-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)-5,6-dihydropyridine-1(2H)-carboxylate収率 32%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

To 5-methoxy-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-ylboronic acid (398 mg, 1.932 mmol) was added sodium carbonate (410 mg, 3.86 mmol), lithium chloride (164 mg, 3.86 mmol), tert-butyl 4-(trifluoromethylsulfonyloxy)-5,6-dihydropyridine-1(2H)-carboxylate (640 mg, 1.932 mmol) and deairared 1,4-Dioxane (15 mL) at rt temperature, followed by tetrakis (triphenylphosphine)pladdinum (0) (112 mg, 0.097 mol), and H2O (1 mL). The resulting light brown mixture was stirred at 80° C. for 2 hr. After cooling down to rt, the mixture was partitioned between H2O/EtOAc (30 mL/50 mL), and separated. The organic layer was washed with brine (10 mL), dried (Na2SO4), concentrated on rotary vacuo, purified on Biotage Flash Collector eluting with 30˜80% EtOAc/Hexanes (1200 mL) to afford the expected product, tert-butyl 4-(5-methoxy-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)-5,6-dihydropyridine-1(2H)-carboxylate (207 mg, 32%). 1H-NMR (400 MHz, MeOD) δ ppm 1.44-1.51 (m, 9 H) 2.51 (d, J=1.51 Hz, 2 H) 3.59 (s, 2 H) 3.78 (s, 3 H) 3.93 (s, 3 H) 4.04 (s, 2 H) 4.86 (s, 1 H) 5.82 (s, 1 H) 6.39 (d, J=2.52 Hz, 1 H) 7.27 (d, J=3.27 Hz, 1 H) 7.58 (s, 1 H); Mass spec 344.18 (MH+) Calc for C19H25N3O3 343.19.

後処理

  1. temperatureAfter cooling down to rt
  2. customthe mixture was partitioned between H2O/EtOAc (30 mL/50 mL)
  3. customseparated
  4. washThe organic layer was washed with brine (10 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated on rotary vacuo
  7. custompurified on Biotage Flash Collector
  8. washeluting with 30˜80% EtOAc/Hexanes (1200 mL)

出典と根拠

ORDレコード
ord-30e7d941217647e09bd33aa851beb2e5
出典データセット
uspto-grants-2008_12
特許番号
US07470680B2

反応ノート

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