Triethylamine → HCID 58869116, compound

HRID 1623142Notes

Reaction equation

HRID 1623142 reaction equation
[CH3:1][O:2][NH:3][CH2:4][CH2:5][CH2:6][CH2:7][N:8]1[C:20]2[C:19]3[N:18]=[CH:17][CH:16]=[CH:15][C:14]=3[N:13]=[C:12]([NH2:21])[C:11]=2[N:10]=[C:9]1[CH2:22][O:23][CH2:24][CH3:25].C(N(CC)CC)C.[CH:33]([N:36]=[C:37]=[O:38])([CH3:35])[CH3:34]>ClCCl.C(=O)(O)[O-].[Na+]>[NH2:21][C:12]1[C:11]2[N:10]=[C:9]([CH2:22][O:23][CH2:24][CH3:25])[N:8]([CH2:7][CH2:6][CH2:5][CH2:4][N:3]([O:2][CH3:1])[C:37]([NH:36][CH:33]([CH3:35])[CH3:34])=[O:38])[C:20]=2[C:19]2[N:18]=[CH:17][CH:16]=[CH:15][C:14]=2[N:13]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 61277Isopropyl isocyanateHCID 86612258HCID 86612258, compound

Product 1

HCID 58869116HCID 58869116, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
-8 °C

Procedure

The preparation of O-methyl-N-[4-(4-amino-2-ethoxymethyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)butyl]-hydroxylamine is described in Parts A-C of Example 20. Triethylamine (0.14 mL, 1.01 mmol) was added to a solution of O-methyl-N-[4-(4-amino-2-ethoxymethyl-1H-imidazo[4,5-c][1,5]naphthyrdin-1-yl)butyl]hydroxylamine (0.29 g, 0.84 mmol) in dichloromethane (8 mL) and cooled to −8° C. Isopropyl isocyanate (0.08 mL, 0.84 mmol) was added dropwise to the reaction mixture, allowed to warm to ambient temperature and was stirred overnight. The reaction mixture was then diluted with dichloromethane (40 mL) and saturated aqueous sodium bicarbonate (30 mL) and the phases were separated. The aqueous phase was extracted with dichloromethane (20 mL) and the combined organic layers were dried over magnesium sulfate, filtered, and concentrated to afford a yellow solid. The material was then purified by HPFC (eluting with 0-25% CMA in chloroform) and crystallized from acetonitrile, filtered, dried at 80° C. in a vacuum oven over the weekend to afford 0.178 g of 1-[4-(4-amino-2-ethoxymethyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)butyl]-3-isopropyl-1-methoxyurea as a white powder, mp 146-147° C. Anal. calcd for C21H31N7O3: C, 58.72; H, 7.27; N, 22.83. Found: C, 58.54; H, 7.27; N, 22.78.

Workup

  1. temperatureto warm to ambient temperature
  2. customthe phases were separated
  3. extractionThe aqueous phase was extracted with dichloromethane (20 mL)
  4. dry with materialthe combined organic layers were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto afford a yellow solid
  8. customThe material was then purified by HPFC (eluting with 0-25% CMA in chloroform)
  9. customcrystallized from acetonitrile
  10. filtrationfiltered
  11. customdried at 80° C. in a vacuum oven over the weekend

Sources & evidence

ORD record
ord-4aadb6f574c24c428f135419e29e3c5c
Source dataset
uspto-grants-2014_07
Patent number
US08778963B2

Reaction notes

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