Ammonia → HCID 57557264, compound

HRID 1798884Notes

Reaction equation

HRID 1798884 reaction equation
C([O:4][CH2:5][C:6]1[N:7]([CH2:20][C:21]([F:24])([CH3:23])[CH3:22])[C:8]2[C:17]3[N:16]=[CH:15][CH:14]=[CH:13][C:12]=3[N:11]=[C:10]([NH2:18])[C:9]=2[N:19]=1)(=O)C.N.C(Cl)Cl>CO>[NH2:18][C:10]1[C:9]2[N:19]=[C:6]([CH2:5][OH:4])[N:7]([CH2:20][C:21]([F:24])([CH3:23])[CH3:22])[C:8]=2[C:17]2[N:16]=[CH:15][CH:14]=[CH:13][C:12]=2[N:11]=1

Participants

5

Reactant 3

HCID 222AmmoniaHCID 6344DichloromethaneHCID 68940335[4-amino-1-(2-fluoro-2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-2-yl]methyl acetate

Product 1

HCID 57557264HCID 57557264, compoundYield 48.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A solution of [4-amino-1-(2-fluoro-2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-2-yl]methyl acetate (1.13 g, 3.41 mmol) dissolved in 10 mL of methanol was treated with 10 mL of a 7% solution of ammonia in methanol. The mixture was stirred for 2 hours and then concentrated under reduced pressure. The resulting solid was treated with H2O and the mixture was heated to reflux for 15 minutes. The mixture was cooled and the resulting light-yellow solid was isolated by filtration. The light-yellow, solid was then treated with 20 mL of CH2Cl2 and the mixture was stirred rapidly for several minutes. The mixture was filtered and the resulting white solid was washed with several portions of cold CH2Cl2 and dried with suction. Crystallization from ethanol/H2O gave 477 mg of [4-amino-1-(2-fluoro-2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-2-yl]methanol as fluffy cream colored crystals, mp 240-241° C. 1H NMR (300 MHz, DMSO-d6) δ 8.50 (dd, J=1.5, 4.3 Hz, 1H), 7.93 (dd, J=1.5, 8.4 Hz, 1H), 7.46 (dd, J=4.3, 8.4 Hz, 1H), 6.92 (s, 2H), 5.62 (t, J=5.8 Hz, 1H), 5.33 (br s, 2H), 4.83 (d, J=4.7 Hz, 2H), 1.33 (d, J=20.3 Hz, 6H); 13C NMR (125 MHz, DMSO-d6) δ 154.3, 152.7, 143.1, 140.8, 134.2, 133.4, 133.2, 128.7, 122.5, 96.8 (d, J=170 Hz), 56.7 (d, J=9.5 Hz), 52.7 (d, J=21.4 Hz), 24.5; MS (ESI) m/z 290 (+H)+; Anal. calcd for C14H16FN5O: C, 58.12; H, 5.57; N, 24.21. Found: C, 58.19; H, 5.54; N, 24.16.

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionThe resulting solid was treated with H2O
  3. temperaturethe mixture was heated
  4. temperatureto reflux for 15 minutes
  5. temperatureThe mixture was cooled
  6. customthe resulting light-yellow solid was isolated by filtration
  7. stirringthe mixture was stirred rapidly for several minutes
  8. filtrationThe mixture was filtered
  9. washthe resulting white solid was washed with several portions of cold CH2Cl2
  10. customdried with suction
  11. customCrystallization from ethanol/H2O

Sources & evidence

ORD record
ord-abd0022287ef45529eefd8fa2075eb8f
Source dataset
uspto-grants-2013_01
Patent number
US08343993B2

Reaction notes

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