Water → 2-(N-Benzyloxycarbonyl-guanidino)-4-Chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid

HRID 1172469Notes

Reaction equation

HRID 1172469 reaction equation
CS/[C:3](=[N:5]\[H])/[NH2:4].[NH2:7][C:8]1[CH:28]=[C:27]([Cl:29])[C:11]2[O:12][C:13]3[C:22]([CH3:23])=[CH:21][C:20]([C:24]([OH:26])=[O:25])=[CH:19][C:14]=3[S:15](=[O:18])(=[O:17])[CH2:16][C:10]=2[CH:9]=1.[OH2:30].CN([CH:34]=[O:35])C>>[CH2:16]([O:30][C:34]([N:7]([C:8]1[CH:28]=[C:27]([Cl:29])[C:11]2[O:12][C:13]3[C:22]([CH3:23])=[CH:21][C:20]([C:24]([OH:26])=[O:25])=[CH:19][C:14]=3[S:15](=[O:17])(=[O:18])[CH2:16][C:10]=2[CH:9]=1)[C:3]([NH2:4])=[NH:5])=[O:35])[C:10]1[CH:11]=[CH:27][CH:28]=[CH:8][CH:9]=1

Participants

5

Reactant 4

HCID 962WaterHCID 6228DimethylformamideHCID 116317172-Amino-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda *6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acidHCID 178506525HCID 178506525, compound

Product 1

HCID 1317284382-(N-Benzyloxycarbonyl-guanidino)-4-Chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acidYield 26.22%

Conditions

Temperature
110 °C

Procedure

Z2-S-methyl isothiourea (0.097 g, 0.27 mmol) was added to the methyl ester of Example 35j (0.1 g, 0.27 mmol) in dry DMF (8 mL) and the reaction mixture was heated at 110° C. for 2 h. It was treated with water and extracted with ethyl acetate. The ethyl acetate layer was concentrated and the solid obtained was purified using flash chromatography (silica gel, EtOAc/PE60-80° C.). The product obtained was then subjected to hydrolysis as described in Example 1i to obtain the title compound. Yield: 26.22%; 1H NMR (DMSO-d6): δ 2.60 (s, 3H, CH3), 5.20 (s, 2H, CH2), 5.30 (s, 2H, SO2—CH2), 7.35 (m, 5H, Ar), 7.70 (s, 2H, Ar), 8.10 (d, 2H, Ar); MS: m/e (EI+) 529 (M+).

Workup

  1. extractionextracted with ethyl acetate
  2. concentrationThe ethyl acetate layer was concentrated
  3. customthe solid obtained
  4. customwas purified
  5. customflash chromatography (silica gel, EtOAc/PE60-80° C.)
  6. customThe product obtained
  7. customwas then subjected to hydrolysis

Sources & evidence

ORD record
ord-8fa43e417aad49879791bfb0cabfddac
Source dataset
uspto-grants-2010_11
Patent number
US07834001B2

Reaction notes

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