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

HRID 81922

反応式

HRID 81922 の反応式
[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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-d7235b8c8d184d2cbba41f110ca62cfe
出典データセット
uspto-grants-2014_09
特許番号
US08846710B2

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