Hydrochloric Acid → HCID 178493316, compound

HRID 1082179Notes

Reaction equation

HRID 1082179 reaction equation
[NH2:1][CH2:2][C:3]1[N:7]=[C:6]([C@H:8]2[NH:21][C:20](=[S:22])[CH2:19][CH2:18][CH2:17][CH2:16][O:15][C:14](=[O:23])[C:13]3[C:24]([CH3:40])=[C:25]([O:38][CH3:39])[CH:26]=[C:27]([O:28][Si](C)(C)C(C)(C)C(C)C)[C:12]=3[CH2:11][S:10][CH2:9]2)[O:5][N:4]=1.P([O-])([O-])([O-])=O.[Na+].[Na+].[Na+].[OH-].[Na+].Cl.[C:52](=[NH:57])(OCC)[CH3:53].Cl>>[OH:28][C:27]1[C:12]2[CH2:11][S:10][CH2:9][C@@H:8]([C:6]3[O:5][N:4]=[C:3]([CH2:2][NH:1][C:52](=[NH:57])[CH3:53])[N:7]=3)[NH:21][C:20](=[S:22])[CH2:19][CH2:18][CH2:17][CH2:16][O:15][C:14](=[O:23])[C:13]=2[C:24]([CH3:40])=[C:25]([O:38][CH3:39])[CH:26]=1

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 24243Trisodium PhosphateHCID 2724290Ethanimidic acid, ethyl ester, hydrochloride (1:1)HCID 53857414HCID 53857414, compound

Product 1

HCID 178493316HCID 178493316, compoundYield 24%

Procedure

The pH of a suspension of 20 mg of the product of Example 130 in 3 ml of 0.05M pH7 sodium phosphate buffer was adjusted to 8.5 by the addition of 0.1N sodium hydroxide. Over 3 h, 74 mg of ethyl acetimidate hydrochloride were added in small portions, the pH of the reaction mixture being maintained at 8.5. The mixture was set to pH 7 by addition of 1N hydrochloric acid and then extracted with ethyl acetate. The aqueous phase was concentrated in vacuo and chromatographed on MCI-Gel CHP20P (Mitsubishi Chemical Industries, Ltd.) using at first 1% aqueous acetic acid and then mixtures of 1% aqueous acetic acid with acetonitrile (10:1 to 2:1, v/v). The product-containing fractions were lyophilized to yield 4 mg of (4R)-N-[5-(16-hydroxy-14-methoxy-13-methyl-12-oxo -6-thioxo-1,3,4,5,6,7,8,9,10,12-decahydro-11,2,5-benzoxathiaazacyclotetradecin-4-yl)-1,2,4-oxadiazol-3-ylmethyl]-acetimidamide hydroacetate.

Workup

  1. temperaturethe pH of the reaction mixture being maintained at 8.5
  2. extractionextracted with ethyl acetate
  3. concentrationThe aqueous phase was concentrated in vacuo
  4. customchromatographed on MCI-Gel CHP20P (Mitsubishi Chemical Industries, Ltd.)

Sources & evidence

ORD record
ord-5231905bf1834539af2891c27f020c6e
Source dataset
uspto-grants-1996_12
Patent number
US05589473

Reaction notes

Loading…