Hydrochloric Acid → HCID 58869117, compound

HRID 1623128Notes

Reaction equation

HRID 1623128 reaction equation
[NH2:1][C:2]1[C:7]2[N:8]=[C:9]([CH2:31][CH2:32][CH3:33])[N:10]([CH2:11][CH2:12][CH2:13][CH2:14][N:15]([O:23]C(OC(C)(C)C)=O)[C:16](=O)[O:17]C(C)(C)C)[C:6]=2[C:5]([CH3:34])=[C:4]([CH3:35])[N:3]=1.Cl.O1CCOC[CH2:38]1.C(N(CC)CC)C.C(OC(=O)C)(=O)C>ClCCl>[NH2:1][C:2]1[C:7]2[N:8]=[C:9]([CH2:31][CH2:32][CH3:33])[N:10]([CH2:11][CH2:12][CH2:13][CH2:14][N:15]([OH:23])[C:16](=[O:17])[CH3:38])[C:6]=2[C:5]([CH3:34])=[C:4]([CH3:35])[N:3]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 312751,4-DioxaneHCID 86612256HCID 86612256, compound2×

Product 1

HCID 58869117HCID 58869117, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The preparation of tert-butyl 4-(4-amino-6,7-dimethyl-2-propyl-1H-imidazo[4,5-c]pyridin-1-yl)butyl[(tert-butoxycarbonyl)oxy]carbamate is described in Parts A-F of Example 14. A solution of 4M hydrochloric acid in dioxane (1.8 mL, 7.2 mmol, 20 eq) is added to a solution of tert-butyl 4-(4-amino-6,7-dimethyl-2-propyl-1H-imidazo[4,5-c]pyridin-1-yl)butyl[(tert-butoxycarbonyl)oxy]carbamate (175 mg, 0.36 mmol, 1.0 eq) in dichloromethane (4 mL) and stirred at ambient temperature for 2 hours. The reaction mixture was concentrated under reduced pressure and the resulting crude material was dissolved in 1-methyl-2-pyrrolidinone (NMP) (4 mL) and cooled to −8° C. Triethylamine (0.500 mL, 10 eq) and acetic anhydride (0.034 mL, 0.36 mmol) were sequentially added dropwise to the reaction mixture and stirred for 1 hour. The crude reaction mixture was concentrated reduced pressure at 70° C. The residue was partitioned between saturated aqueous sodium carbonate and chloroform and the phases were separated. The aqueous phase was back-extracted with chloroform and the combined organics were dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford crude material. The material was purified by column chromatography on a BIOTAGE HORIZON High-Performance Flash Chromatography instrument (silica gel, eluting with 10-50% CMA in chloroform) and trituration with chloroform/ethyl acetate. The resulting material was filtered and washed with ethyl acetate and dried under high vacuum to afford 0.025 g of N-[4-(4-amino-6,7-dimethyl-2-propyl-1H-imidazo[4,5-c]pyridin-1-yl)butyl]-N-hydroxyacetamide as a white powder, mp 164.0-166.0° C. MS (APCI) m/z 334 (M)+; Anal. Calcd for C17H27N5O2.0.05CHCl3 C, 60.34; H, 8.03; N, 20.64. Found: C, 60.05; H, 7.97; N, 20.43.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe resulting crude material was dissolved in 1-methyl-2-pyrrolidinone (NMP) (4 mL)
  3. temperaturecooled to −8° C
  4. stirringstirred for 1 hour
  5. customThe crude reaction mixture
  6. concentrationwas concentrated reduced pressure at 70° C
  7. customThe residue was partitioned between saturated aqueous sodium carbonate and chloroform
  8. customthe phases were separated
  9. extractionThe aqueous phase was back-extracted with chloroform
  10. dry with materialthe combined organics were dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customto afford crude material
  14. customThe material was purified by column chromatography on a BIOTAGE HORIZON High-Performance Flash Chromatography instrument (silica gel, eluting with 10-50% CMA in chloroform) and trituration with chloroform/ethyl acetate
  15. filtrationThe resulting material was filtered
  16. washwashed with ethyl acetate
  17. customdried under high vacuum

Sources & evidence

ORD record
ord-df9705b07306437593ef665ed743f614
Source dataset
uspto-grants-2014_07
Patent number
US08778963B2

Reaction notes

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