Hydrochloric Acid → (4-amino-1-{4-[(methylsulfonyl)amino]butyl}-1H-imidazo[4,5-c]quinolin-2-yl)methyl L-valinate

HRID 81923

Reaction equation

HRID 81923 reaction equation
C(OC([NH:11][C@H:12]([C:16]([O:18][CH2:19][C:20]1[N:21]([CH2:34][CH2:35][CH2:36][CH2:37][NH:38][S:39]([CH3:42])(=[O:41])=[O:40])[C:22]2[C:31]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[N:25]=[C:24]([NH2:32])[C:23]=2[N:33]=1)=[O:17])[CH:13]([CH3:15])[CH3:14])=O)C1C=CC=CC=1.CO.C1COCC1.Cl>[Pd].O>[NH2:11][C@H:12]([C:16]([O:18][CH2:19][C:20]1[N:21]([CH2:34][CH2:35][CH2:36][CH2:37][NH:38][S:39]([CH3:42])(=[O:40])=[O:41])[C:22]2[C:31]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[N:25]=[C:24]([NH2:32])[C:23]=2[N:33]=1)=[O:17])[CH:13]([CH3:15])[CH3:14]

Participants

7

Reactant 4

HCID 313Hydrochloric Acid2×HCID 887MethanolHCID 8028TetrahydrofuranHCID 57555848(4-amino-1-{4-[(methylsulfonyl)amino]butyl}-1H-imidazo[4,5-c]quinolin-2-yl)methyl N-[(benzyloxy)carbonyl]-L-valinate

Product 1

HCID 57555835(4-amino-1-{4-[(methylsulfonyl)amino]butyl}-1H-imidazo[4,5-c]quinolin-2-yl)methyl L-valinateYield 42.8%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst2×HCID 962WaterSolvent

Procedure

To a hydrogenation bottle was added (4-amino-1-{4-[(methylsulfonyl)amino]butyl}-1H-imidazo[4,5-c]quinolin-2-yl)methyl N-[(benzyloxy)carbonyl]-L-valinate (1.5 g, 2.5 mmol) followed by a mixture of methanol (30 mL), THF (15 mL) and water (5 mL) and conc HCl (5 mL). To this was added Pd/C (90 mg) and the reaction was hydrogenated at 40 psi (2.8×105 Pa) overnight. To the reaction mixture was added conc. HCl (5 mL) and Pd/C (90 mg) and the reaction was hydrogenated at 40 psi (2.8×105 Pa) for 18 hours. The reaction was filtered through CELITE filter aid and the filtrate was evaporated to afford a clear oil. The product was isolated by prep HPLC (ISCO Combiflash Separation System, Biotage Si 40+M column, eluted with a gradient of 0-8% methanol in dichloromethane with 1% ammonium hydroxide) to provide (4-amino-1-{4-[(methylsulfonyl)amino]butyl}-1H-imidazo[4,5-c]quinolin-2-yl)methyl L-valinate (0.495 g) as an off white solid, mp 161-163° C.; MS (ESI) m/z 463 (M+H)+; Anal. Calcd for C21H30N6O4S: C, 54.53; H, 6.54; N, 18.17. Found C, 53.96; H, 6.62; N, 17.85, delta C=0.57.

Workup

  1. customwas hydrogenated at 40 psi (2.8×105 Pa) overnight
  2. filtrationThe reaction was filtered through CELITE
  3. filtrationfilter aid
  4. customthe filtrate was evaporated
  5. customto afford a clear oil
  6. customThe product was isolated by prep HPLC (
  7. customISCO Combiflash Separation System, Biotage Si 40+M column
  8. washeluted with a gradient of 0-8% methanol in dichloromethane with 1% ammonium hydroxide)

Sources & evidence

ORD record
ord-dfc6e069e2304a62ad9469b5fddf58b4
Source dataset
uspto-grants-2014_09
Patent number
US08846710B2

Linked notes

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