Dimethylformamide → HCID 13002104, compound

HRID 1106185Notes

Reaction equation

HRID 1106185 reaction equation
[NH:1]1[C:5](=[O:6])[CH2:4][CH2:3][C@H:2]1[C:7]([OH:9])=O.S(Cl)(Cl)=O.CN(C=O)C.[NH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[NH:27][C:28](=[O:35])[C:29](=[CH:33][CH:34]=2)[C:30]([OH:32])=[O:31])=[CH:22][CH:21]=1.C(N(CC)CC)C.Cl[Si](C)(C)C>ClCCl>[NH:1]1[C:5](=[O:6])[CH2:4][CH2:3][C@H:2]1[C:7]([NH:19][C:20]1[CH:21]=[CH:22][C:23]([C:26]2[NH:27][C:28](=[O:35])[C:29](=[CH:33][CH:34]=2)[C:30]([OH:32])=[O:31])=[CH:24][CH:25]=1)=[O:9]

Participants

8

Reactant 6

HCID 6228DimethylformamideHCID 6397ChlorotrimethylsilaneHCID 7405L-Pyroglutamic AcidHCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 129189566-(4-Aminophenyl)-1,2-dihydro-2-oxonicotinic acid

Product 1

HCID 13002104HCID 13002104, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 2.3 g (5.75 m mol) of the above enamine and 20 ml of DMF is stirred at room temperature and 2.3 g (14.2 m mol) of carbonyldiimidazole is added. The solution is stirred at 50°-60° for 1 hr and then at room temperature overnight. The DMF is evaporated under vacuum and the residue dissolved in 40 ml of dichloromethane. The solution is diluted with 100 ml of ethyl acetate and 100 ml of ether. The precipitated solid is filtered, washed with 1:1 ethyl acetate ether and ether and dried to give 2.2 g of imidazolide. L. A mixture of 19.37 g (0.15 mol) of L-pyroglutamic acid, 11.0 ml (0.15 mol) of thionyl chloride, 11.6 ml (0.15 mol) of DMF, and 350 ml of dichloromethane is stirred at 0°-5° for 70 min. This solution is then added to a cold solution of the silylated derivative of 6-(4-aminophenyl)-1,2-dihydro-2-oxonicotinic acid prepared by the method of Starting Material I from 23 g (0.1 mol) of the acid, 42 ml (0.3 mol) of triethylamine, 38 ml (0.3 mol) of chlorotrimethylsilane, and 750 ml of dichloromethane. The reaction mixture is stirred at 0°-5° for 1 hr 45 min and then evaporated to dryness. Methanol is added to the residue and evaporated again. Next 500 ml of methanol and 500 ml of water are added and the solid is collected by filtration, washed with warm methanol and with ether. Drying gives 27.84 g of 6-[4-(L-pyroglutamylamino)phenyl]-1,2-dihydro-2-oxonicotinic acid; [α]D23 +15.2 (cl, DMSO).

Workup

  1. stirringThe reaction mixture is stirred at 0°-5° for 1 hr 45 min
  2. customevaporated to dryness
  3. additionMethanol is added to the residue
  4. customevaporated again
  5. additionNext 500 ml of methanol and 500 ml of water are added
  6. filtrationthe solid is collected by filtration
  7. washwashed with warm methanol and with ether
  8. customDrying

Sources & evidence

ORD record
ord-6eee82f338204f78b8200ea5fe1cebf1
Source dataset
uspto-grants-1982_01
Patent number
US04311698

Reaction notes

Loading…