Hydrochloric Acid → (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-(3,4-dihydroxyphenyl)sulfonylethoxyimino]acetyl]amino]-3-[[2-(hydroxymethyl)-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl]sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

HRID 846913Notes

Reaction equation

[NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:37]/[O:38][CH2:39][CH2:40]I)/[C:8]([NH:10][C@@H:11]2[C:18](=[O:19])[N:17]3[C@@H:12]2[S:13][CH2:14][C:15]([CH2:23][S:24][C:25]2[N:30]4[N:31]=[C:32]([CH2:34][OH:35])[N:33]=[C:29]4[N:28]=[C:27]([CH3:36])[CH:26]=2)=[C:16]3[C:20]([OH:22])=[O:21])=[O:9])[N:6]=1.[Li+].C1(C2(C3C=CC=CC=3)[O:53][C:52]3[CH:54]=[CH:55][C:56]([S:58]([O-:60])=[O:59])=[CH:57][C:51]=3[O:50]2)C=CC=CC=1.C(=O)([O-])O.[Na+].Cl>CN(C)C=O.O>[NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:37]/[O:38][CH2:39][CH2:40][S:58]([C:56]2[CH:55]=[CH:54][C:52]([OH:53])=[C:51]([OH:50])[CH:57]=2)(=[O:60])=[O:59])/[C:8]([NH:10][C@@H:11]2[C:18](=[O:19])[N:17]3[C@@H:12]2[S:13][CH2:14][C:15]([CH2:23][S:24][C:25]2[N:30]4[N:31]=[C:32]([CH2:34][OH:35])[N:33]=[C:29]4[N:28]=[C:27]([CH3:36])[CH:26]=2)=[C:16]3[C:20]([OH:22])=[O:21])=[O:9])[N:6]=1

Participants

Conditions

Temperature: 20 °C

Procedure

A mixture of 146 mg of (6R, 7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-[(2-iodoethoxy)imino]acetamido]-3-[[[2-(hydroxymethyl)-5-methyl-s-triazolo[1,5-a]pyrimidin-7-yl]thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 75 mg of 2,2-diphenyl-1,3-benzodioxol-5-sulphinic acid lithium salt and 24 mg of sodium hydrogen carbonate in 0.5 ml of N,N-dimethylformamide was stirred at 20° C. for 24 hours. The reaction mixture was treated with 5 ml of water and the pH of the mixture was lowered to 3 by the addition of 3N hydrochloric acid. The resulting precipitate was filtered off under suction, washed with a small amount of water and then dissolved in 4 ml of water with the addition of small amount of 2N sodium hydroxide solution. This solution, of pH 7.5, was applied to a MCI gel column (CHP2OP) conditioned with 1 % aqueous acetic acid and chromatographed according to the procedure described in Example 16. The fraction eluted with a 1:1 (v/v) water/acetonitrile mixture was concentrated in a vacuum and lyophilized. The lyophilizate was dissolved in 90% aqueous trifluoroacetic acid and the solution was stirred at 20° C. for 20 minutes. The solvents were removed in a vacuum and the residue was partitioned between ethyl acetate and 2% sodium hydrogen carbonate solution. The aqueous phase was chromatographed according to the procedure described in Example 16. After concentration and lyophilization of the pure fractions, there was obtained (6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-[[2-[(3,4-dihydroxyphenyl)-sulphonyl]ethoxy]imino]acetamido]-3-[[[2-(hydroxymethyl)-5-methyl-s-triazolo[1,5-a]pyrimidin-7-yl]thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid as a white powder.

Workup

filtrationThe resulting precipitate was filtered off under suction
washwashed with a small amount of water
dissolutiondissolved in 4 ml of water with the addition of small amount of 2N sodium hydroxide solution
customchromatographed
washThe fraction eluted with a 1:1 (v/v) water/acetonitrile mixture
concentrationwas concentrated in a vacuum
dissolutionThe lyophilizate was dissolved in 90% aqueous trifluoroacetic acid
stirringthe solution was stirred at 20° C. for 20 minutes
customThe solvents were removed in a vacuum
customthe residue was partitioned between ethyl acetate and 2% sodium hydrogen carbonate solution
customThe aqueous phase was chromatographed
concentrationAfter concentration and lyophilization of the pure fractions

Sources & evidence

ORD record: ord-5ba3e8e4300945fe9415251bd1d9bfdf
Source dataset: uspto-grants-1992_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05138066

Reaction notes

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