Trifluoroacetic acid → HCID 58227661, compound

HRID 1363601Notes

Reaction equation

HRID 1363601 reaction equation
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:22][CH2:23][CH3:24])[N:14]([CH2:15][C:16]3([OH:21])[CH2:20][CH2:19][CH2:18][CH2:17]3)[C:10]=2[C:9]2[N:8]=[CH:7][CH:6]=[CH:5][C:4]=2[N:3]=1.FC(F)(F)C(O)=O>[Pt]=O>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:22][CH2:23][CH3:24])[N:14]([CH2:15][C:16]3([OH:21])[CH2:17][CH2:18][CH2:19][CH2:20]3)[C:10]=2[C:9]2[NH:8][CH2:7][CH2:6][CH2:5][C:4]=2[N:3]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 58227628HCID 58227628, compound

Product 1

HCID 58227661HCID 58227661, compoundYield 32.3%

Reagents, catalysts & solvents 1

HCID 82844Platinum oxide (PtO)Catalyst

Procedure

A mixture of 1-[(4-amino-2-propyl-1H-imidazo[4,5-c][1,5]napthyridin-1-yl)methyl]cyclopentanol (511 mg), platinum oxide (511 mg), and trifluoroacetic acid was placed under hydrogen pressure (50 psi, 3.4×105 Pa) overnight on a Parr apparatus. The mixture was filtered through a layer of CELITE filter aid and the filter cake was rinsed with methanol. The filtrate was concentrated under reduced pressure. The residue was combined with concentrated hydrochloric acid (2 mL) and stirred at ambient temperature for 2 hours. The mixture was diluted with water (10 mL) and then cooled to 0° C. The pH was adjusted to 12 with 6N sodium hydroxide and then the mixture was extracted with dichloromethane (3×50 mL). The combined organics were washed with brine (20 mL), dried over sodium sulfate, filtered, and then concentrated under reduced pressure. The residue was triturated with acetonitrile, purified by HPFC eluting with a gradient of 0-35% CMA in chloroform, and then triturated with acetonitrile to provide 167 mg of 1-[(4-amino-2-propyl-6,7,8,9-tetrahydro-1H-imidazo[4,5-c][1,5]napthyridin-1-yl)methyl]cyclopentanol as a white powder, mp 207.0-208.0° C. Anal. Calcd for C18H27N5O.0.25H2O C, 64.74; H, 8.30; N, 20.97. Found: C, 64.71; H, 8.29; N, 20.98.

Workup

  1. custompressure (50 psi, 3.4×105 Pa) overnight
  2. filtrationThe mixture was filtered through a layer of CELITE
  3. filtrationfilter aid
  4. washthe filter cake was rinsed with methanol
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. additionThe mixture was diluted with water (10 mL)
  7. temperaturecooled to 0° C
  8. extractionthe mixture was extracted with dichloromethane (3×50 mL)
  9. washThe combined organics were washed with brine (20 mL)
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customThe residue was triturated with acetonitrile
  14. custompurified by HPFC
  15. washeluting with a gradient of 0-35% CMA in chloroform
  16. customtriturated with acetonitrile

Sources & evidence

ORD record
ord-ad207c6bca2d48f19d57e3602e05901f
Source dataset
uspto-grants-2011_02
Patent number
US07884207B2

Reaction notes

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