Chlorotrimethylsilane → 6-[4-(N,N'-bis(benzyloxycarbonyl)-L-lysylamino)phenyl]-1,2-dihydro-2-oxonicotinic acid

HRID 1106190Notes

Reaction equation

HRID 1106190 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:28]([OH:30])=O)[CH2:13][CH2:14][CH2:15][CH2:16][NH:17][C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN1CCOCC1.ClC(OCC(C)C)=O.[NH2:46][C:47]1[CH:52]=[CH:51][C:50]([C:53]2[NH:54][C:55](=[O:62])[C:56](=[CH:60][CH:61]=2)[C:57]([OH:59])=[O:58])=[CH:49][CH:48]=1.C(N(CC)CC)C.Cl[Si](C)(C)C>ClCCl>[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:28]([NH:46][C:47]1[CH:48]=[CH:49][C:50]([C:53]2[NH:54][C:55](=[O:62])[C:56](=[CH:60][CH:61]=2)[C:57]([OH:59])=[O:58])=[CH:51][CH:52]=1)=[O:30])[CH2:13][CH2:14][CH2:15][CH2:16][NH:17][C:18]([O:20][CH2:21][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)=[O:19])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 6

HCID 6397ChlorotrimethylsilaneHCID 79724-MethylmorpholineHCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 7269422N2,N6-Bis[(phenylmethoxy)carbonyl]-L-lysineHCID 129189566-(4-Aminophenyl)-1,2-dihydro-2-oxonicotinic acid

Product 1

HCID 130021166-[4-(N,N'-bis(benzyloxycarbonyl)-L-lysylamino)phenyl]-1,2-dihydro-2-oxonicotinic acidYield 75.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 29.0 g (70 mmol) of N,N'-bis(benzyloxycarbonyl)-L-lysine [Helv. Chem. Acta, 41, 1778 (1958)] in 200 ml of dichloromethane is stirred at -10° and 7.2 g (70 mmol) of N-methylmorpholine is added. The temperature is lowered to -14° and 9.55 g (70 mmol) of isobutyl chloroformate is added dropwise over a period of 10 min and stirring is continued at -14° to -11° for 40 min. A suspension of 8.0 g (35 mmol) of 6-(4-aminophenyl)-1,2-dihydro-2-oxonicotinic acid, 10.5 g (35 mmol) of triethylamine and 200 ml of dichloromethane is stirred at 5° and 12.0 g (35 mmol) of chlorotrimethylsilane is added. After 1 hr at room temperature this solution is added over a period of 30 min at -12° to -14° to the mixed anhydride formed above. After 3 hrs at 0°, the solution is allowed to stir overnight at room temperature. The reaction mixture is filtered and the filtrate is stirred with 15 ml of isopropanol for 30 min. The resulting yellow precipitate is filtered, washed, and dried to give 16.6 g of 6-[4-(N,N'-bis(benzyloxycarbonyl)-L-lysylamino)phenyl]-1,2-dihydro-2-oxonicotinic acid; mp 199°-200°, [α]D23 +24.2° (cl, DMSO).

Workup

  1. customis lowered to -14°
  2. stirringis stirred at 5°
  3. customformed above
  4. waitAfter 3 hrs at 0°
  5. stirringto stir overnight at room temperature
  6. filtrationThe reaction mixture is filtered
  7. stirringthe filtrate is stirred with 15 ml of isopropanol for 30 min
  8. filtrationThe resulting yellow precipitate is filtered
  9. washwashed
  10. customdried

Sources & evidence

ORD record
ord-5b216bea0967489b8a968c57f381ef13
Source dataset
uspto-grants-1982_01
Patent number
US04311698

Reaction notes

Loading…