Potassium Sodium Tartrate → 1-((5-Bromopyridin-3-yloxy)methyl)cyclopropanamine

HRID 2077591

반응식

HRID 2077591 반응식
[Br:1][C:2]1[CH:3]=[C:4]([O:8][CH2:9][C:10]#[N:11])[CH:5]=[N:6][CH:7]=1.[CH2:12]([Mg]Br)[CH3:13].[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([O:8][CH2:9][C:10]2([NH2:11])[CH2:13][CH2:12]2)[CH:5]=[N:6][CH:7]=1

참가 물질

6

반응물 3

HCID 9357Potassium Sodium TartrateHCID 642056672-[(5-Bromopyridin-3-yl)oxy]acetonitrileHCID 178418443HCID 178418443, 화합물

생성물 1

HCID 670976771-((5-Bromopyridin-3-yloxy)methyl)cyclopropanamine수율 19%

시약·촉매·용매 2

HCID 11026Titanium isopropoxide촉매HCID 8028Tetrahydrofuran용매3회

실험 절차

A dry, 10 mL round bottom flask was charged with 2-(5-bromopyridin-3-yloxy)acetonitrile (0.0996 g, 0.47 mmol), 3 mL dry THF, and a stirbar. The flask was fitted with an inert atmosphere inlet, and swept with Ar for several minutes. The solution was treated with titanium isopropoxide (0.15 ml, 0.51 mmol). To the stirring solution was added ethylmagnesium bromide 1.0 m solution in the (0.94 ml, 0.94 mmol) via a syringe pump over 30 minutes. The reaction was stirred at room temperature for 24 h after which time 1 mL of saturated Rochelle's salt was added, followed by 5 mL dry THF. The slurry was stirred/sonicated over the course of 1 h. The solution was then applied to 20 g of SiO2 wet packed with THF. The Silica was eluted with 75 mL dry THF, and the eluent was concentrated in vacuo. The crude was purified using a 19×150 mm Waters Xterra Prep C18 OBD column (100 Å pore diameter, 5 μm particle size, spherical shape, PN 186002381; Gradient: 0→5 min@20 mL/min, 10% B; 5.0→35 min@20 mL/min, linear gradient to 40% B; 35→45@20 mL/min, isocratic at 40% B, 45→55 min@20 mL/min, step to 100% B; 55→60 min@20 mL/min, step to 10% B; 60 min end; A=10.7 mM NH4HCO3 in water, pH adjusted to 8.6 with concentrated NH4OH; B acetonitrile). A band that eluted from 16.1 to 18.3 minutes was isolated. The solvent was removed in vacuo to afford 1-((5-bromopyridin-3-yloxy)methyl)cyclopropanamine (0.0214 g, 19% yield). 1H NMR (400 MHz, chloroform-d) δ ppm 0.64-0.67 (m, 2H) 0.77-0.81 (m, 2H) 1.78 (br. s., 2H) 3.88 (s, 2H) 7.37 (dd, J=2.54, 1.86 Hz, 1H) 8.26 (d, J=2.54 Hz, 1H) 8.29 (d, J=1.86 Hz, 1H). 13C NMR (101 MHz, chloroform-d) δ ppm 12.89 (s, 2 C) 33.49 (s, 1 C) 77.00 (s, 1 C) 120.35 (s, 1 C) 124.03 (s, 1 C) 136.43 (s, 1 C) 143.07 (s, 1 C) 155.53 (s, 1 C). HPLC-MS: retention time=0.87 min (>99%@215 nm; >99% @254 nm; m/z=242.9, calculated for C9H1179BrN2O+H+=243.0; m/z=244.9, calculated for C9H1181BrN2O+H+=245.0).

후처리

  1. customThe flask was fitted with an inert atmosphere inlet
  2. waitswept with Ar for several minutes
  3. additionwas added
  4. customThe slurry was stirred/sonicated over the course of 1 h
  5. washThe Silica was eluted with 75 mL dry THF
  6. concentrationthe eluent was concentrated in vacuo
  7. customThe crude was purified
  8. custom0→5 min@20 mL/min, 10% B
  9. custom5.0→35 min@20 mL/min, linear gradient
  10. customisocratic at 40% B, 45→55 min@20 mL/min, step
  11. custom55→60 min@20 mL/min, step
  12. custom60 min end
  13. washA band that eluted from 16.1 to 18.3 minutes
  14. customwas isolated
  15. customThe solvent was removed in vacuo

출처 및 근거

ORD 기록
ord-7c315e4c15084b43be8bbd614070b919
출처 데이터셋
uspto-grants-2011_04
특허 번호
US07928140B2

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