Water → N-[4-amino-5-cyano-6-(2-hydroxyethoxy)pyridin-2-yl]-2-(2,5-dimethoxyphenyl)acetamide

HRID 1364523

反応式

HRID 1364523 の反応式
[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([O:10][CH2:11][CH2:12][OH:13])[N:5]=[C:4]([NH2:14])[CH:3]=1.NC1C(C#N)=C(OC(C)C)N=C(N[C:29](=[O:41])[CH2:30][C:31]2[CH:36]=[C:35]([O:37][CH3:38])[CH:34]=[CH:33][C:32]=2[O:39][CH3:40])C=1.O.[OH-].[Na+]>N1C=CC=CC=1.C(Cl)Cl.C1COCC1>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([O:10][CH2:11][CH2:12][OH:13])[N:5]=[C:4]([NH:14][C:29](=[O:41])[CH2:30][C:31]2[CH:36]=[C:35]([O:37][CH3:38])[CH:34]=[CH:33][C:32]=2[O:39][CH3:40])[CH:3]=1

参加物

8

反応物 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 11610382N-(4-amino-5-cyano-6-isopropoxypyridin-2-yl)-2-(2,5-dimethoxyphenyl)acetamideHCID 669208504,6-Diamino-2-(2-hydroxy-ethoxy)-nicotinonitrile

生成物 1

HCID 11559766N-[4-amino-5-cyano-6-(2-hydroxyethoxy)pyridin-2-yl]-2-(2,5-dimethoxyphenyl)acetamide収率 5.4%

試薬・触媒・溶媒 3

HCID 1049Pyridine溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 39 mg (0.20 mmol) of 4,6-diamino-2-(2-hydroxy-ethoxy)-nicotinonitrile in 0.2 mL of pyridine and 1 mL of CH2Cl2 was added 75 mg (0.39 mmol) of 2,5-dimethoxyphenylacetyl chloride (Example 60B). The mixture was stirred at ambient temperature for 1 hours then 1 mL of water was added, and the solvents were removed under reduced pressure. The residue was taken up in 10 mL of ethyl acetate, then extracted with 1M HCl(aq.) (2×5 mL), saturated NaHCO3(aq.) (2×5 mL), and brine (1×5 mL), dried over MgSO4, filtered, and concentrated to an oil. This was dissolved in 1:1 DMSO:methanol and purified by reversed phase HPLC, eluting with a 5-100% CH3CN gradient in 0.01M NH4OAc(aq.) to provide a white solid. This was dissolved in 1 mL of THF, and 1 mL of 2M NaOH(aq.) was added. The solution was stirred at ambient temperature for 18 hours then concentrated under reduced pressure. The residue was taken up in 10 mL of ethyl acetate, then extracted with water (1×3 mL), 2M NaOH(aq.) (1×3 mL), and brine (1×3 mL), dried over MgSO4, filtered, and concentrated under reduced pressure to a white solid. This was recrystallized from 1 mL of methanol to provide 4 mg (5%) of a white solid. 1H NMR (300 MHz, d6-DMSO) δ 10.10 (s, 11H), 7.13 (s, 1H), 6.90 (m, 3H), 6.79 (m, 2H), 4.81 (t, 1H, J=5.4 Hz), 4.31 (m, 2H), 3.69 (m, 8H), 3.66 (s, 2H); MS (ESI) m/e=329 (M−EtOH+H)+, 373 (M+H)+, 371 (M−H)−.

後処理

  1. customthe solvents were removed under reduced pressure
  2. extractionextracted with 1M HCl(aq.) (2×5 mL), saturated NaHCO3(aq.) (2×5 mL), and brine (1×5 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated to an oil
  6. dissolutionThis was dissolved in 1:1 DMSO
  7. custommethanol and purified by reversed phase HPLC
  8. washeluting with a 5-100% CH3CN gradient in 0.01M NH4OAc(aq.)
  9. customto provide a white solid
  10. stirringThe solution was stirred at ambient temperature for 18 hours
  11. concentrationthen concentrated under reduced pressure
  12. extractionextracted with water (1×3 mL), 2M NaOH(aq.) (1×3 mL), and brine (1×3 mL)
  13. dry with materialdried over MgSO4
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure to a white solid
  16. customThis was recrystallized from 1 mL of methanol

出典と根拠

ORDレコード
ord-a9731edbe57041508f4c055b6163a6f6
出典データセット
uspto-grants-2011_02
特許番号
US07888374B2

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