1,2-Dichloroethane → N-{[3-(9-Chloro-3-methyl-4-oxo-5H-isoxazolo[4,3-c]quinolin-5-yl) cyclohexylcarbamoyl]-methyl}-2-phenyl-acetamide

HRID 352247Notes

Reaction equation

HRID 352247 reaction equation
I.[NH2:2][CH:3]1[CH2:8][CH2:7][CH2:6][CH:5]([N:9]2[C:18]3[CH:17]=[CH:16][CH:15]=[C:14]([Cl:19])[C:13]=3[C:12]3=[N:20][O:21][C:22]([CH3:23])=[C:11]3[C:10]2=[O:24])[CH2:4]1.[CH2:25](Cl)[CH2:26]Cl.ON1[C:34]2N=C[CH:37]=[CH:38][C:33]=2N=N1.C(N(CC)C(C)C)(C)C.Cl.[CH2:49]([NH:56][CH2:57][C:58]([OH:60])=O)[C:50]1C=CC=CC=1.CN(C=[O:65])C>CN(C1C=CN=CC=1)C>[Cl:19][C:14]1[C:13]2[C:12]3[C:11](=[C:22]([CH3:23])[O:21][N:20]=3)[C:10](=[O:24])[N:9]([CH:5]3[CH2:6][CH2:7][CH2:8][CH:3]([NH:2][C:58]([CH2:57][NH:56][C:49](=[O:65])[CH2:50][C:26]4[CH:25]=[CH:37][CH:38]=[CH:33][CH:34]=4)=[O:60])[CH2:4]3)[C:18]=2[CH:17]=[CH:16][CH:15]=1

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 2756624N-Benzylglycine HydrochlorideHCID 227137135-(3-Aminocyclohexyl)-9-chloro-3-methyl-5H-isoxazolo[4,3-c]quinolin-4-one hydroiodide

Product 1

HCID 22714202N-{[3-(9-Chloro-3-methyl-4-oxo-5H-isoxazolo[4,3-c]quinolin-5-yl) cyclohexylcarbamoyl]-methyl}-2-phenyl-acetamide

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Procedure

5-(3-Amino-cyclohexyl)-9-chloro-3-methyl-5H-isoxazolo[4,3-c]quinolin-4-one hydroiodide (70 mg, 0.19 mmol) was combined with EDC (47 mg, 0.25 mmol), 1-hydroxy-7-azabenzo-triazole (34 mg, 0.25 mmol), N,N-diisopropylethyl amine (0.10 mL, 0.58 mmol), DMAP (5 mg, cat.), and N-benzylglycine hydrochloride (50 mg, 0.25 mmol) in DMF(6 mL) and the mixture stirred overnight at rt. The mixture was then concentrated in vacuo and the residue taken up in chloroform/MeOH and the organic solution washed with aqueous NaHCO3. The organic solution was dried over Na2SO4 and concentrated in vacuo. The residue was loaded onto a silica gel column and eluted with MeOH/CH2Cl2, which allowed for the recovery of 32 mg (35%) of the free base. This material was dissolved in minimal EtOAc and treated with excess diethyl ether/hydrochloric acid. Concentration of this mixture to dryness allowed for quantitative recovery of the hydrochloride salt as an off white solid. MS(ES): (M+1)+ 479.1, 481.2.

Workup

  1. concentrationThe mixture was then concentrated in vacuo
  2. washthe organic solution washed with aqueous NaHCO3
  3. dry with materialThe organic solution was dried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. washeluted with MeOH/CH2Cl2, which
  6. dissolutionThis material was dissolved in minimal EtOAc
  7. additiontreated with excess diethyl ether/hydrochloric acid

Sources & evidence

ORD record
ord-19d124634a7d4058a800422b47c9ed87
Source dataset
uspto-grants-2004_06
Patent number
US06743794B2

Reaction notes

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