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

HRID 81922

Reaction equation

HRID 81922 reaction equation
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:24][OH:25])[N:14]([CH2:15][CH2:16][CH2:17][CH2:18][NH:19][S:20]([CH3:23])(=[O:22])=[O:21])[C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[N:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:45]([NH:55][C@H:56]([C:60](O)=[O:61])[CH:57]([CH3:59])[CH3:58])([O:47][CH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)=[O:46].N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1.C(OCC)C>[CH2:48]([O:47][C:45]([NH:55][C@H:56]([C:60]([O:25][CH2:24][C:13]1[N:14]([CH2:15][CH2:16][CH2:17][CH2:18][NH:19][S:20]([CH3:23])(=[O:22])=[O:21])[C:10]2[C:9]3[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=3[N:3]=[C:2]([NH2:1])[C:11]=2[N:12]=1)=[O:61])[CH:57]([CH3:59])[CH3:58])=[O:46])[C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 726987N-Carbobenzoxy-L-valineHCID 11856399N-[4-(4-amino-2-hydroxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]methanesulfonamide

Product 1

HCID 57555848(4-amino-1-{4-[(methylsulfonyl)amino]butyl}-1H-imidazo[4,5-c]quinolin-2-yl)methyl N-[(benzyloxy)carbonyl]-L-valinateYield 57.8%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred suspension of N-[4-(4-amino-2-hydroxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]methanesulfonamide (2.1 g, 5.8 mmol) in THF was added triphenylphosphine (1.5 equivalents, 8.7 mmol, 2.2 g) followed by CBZ-L-valine (1.5 equivalents, 8.7 mmol, 2.3 g). The suspension was stirred for 5 min after which it was cooled in an ice-bath. To this cooled reaction mixture diisopropyl azodicarboxylate (DIAD, 1.8 equivalents, 10.4 mmol, 2.0 mL) was added and the reaction was warmed to room temperature and stirred overnight. The solvent was evaporated under reduced pressure and the crude solid was purified 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 a solid. The solid was heated in diethyl ether and filtered to afford (4-amino-1-{4-[(methylsulfonyl)amino]butyl}-1H-imidazo[4,5-c]quinolin-2-yl)methyl N-[(benzyloxy)carbonyl]-L-valinate (2 g) as a beige solid, mp 99-100° C.; MS (ESI) m/z 597 (M+H)+; Anal. Calcd for C29H36N6O6S: C, 58.37; H, 6.08; N, 14.08. Found C, 57.98; H, 6.31; N, 13.82.

Workup

  1. temperaturewas cooled in an ice-bath
  2. additionwas added
  3. stirringstirred overnight
  4. customThe solvent was evaporated under reduced pressure
  5. customthe crude solid was purified by prep HPLC (
  6. customISCO Combiflash Separation System, Biotage Si 40+M column
  7. washeluted with a gradient of 0-8% methanol in dichloromethane with 1% ammonium hydroxide)
  8. customto provide a solid
  9. filtrationfiltered

Sources & evidence

ORD record
ord-d7235b8c8d184d2cbba41f110ca62cfe
Source dataset
uspto-grants-2014_09
Patent number
US08846710B2

Linked notes

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