Tetrahydrofuran → benzhydryl (6R,7R)-7-[[(2Z)-2-(2-methoxypropan-2-yloxyimino)-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-3-[(7-methyl-5-oxo-[1,3,4]thiadiazolo[3,2-a]pyrimidin-2-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 1905106Notes

Reaction equation

HRID 1905106 reaction equation
[C:1]1([CH:7]([O:14][C:15]([C:17]2[N:18]3[C@H:21]([S:22][CH2:23][C:24]=2[CH2:25][S:26][C:27]2[S:37][C:30]4=[N:31][C:32]([CH3:36])=[CH:33][C:34](=[O:35])[N:29]4[N:28]=2)[C@H:20]([NH2:38])[C:19]3=[O:39])=[O:16])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:40]1([C:46]([NH:59][C:60]2[S:61][CH:62]=[C:63](/[C:65](=[N:69]/[O:70][C:71]([O:74][CH3:75])([CH3:73])[CH3:72])/[C:66](O)=[O:67])[N:64]=2)([C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=2)[C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.O1CCCC1.C1(N=C=NC2CCCCC2)CCCCC1>ClCCl>[C:1]1([CH:7]([O:14][C:15]([C:17]2[N:18]3[C@H:21]([S:22][CH2:23][C:24]=2[CH2:25][S:26][C:27]2[S:37][C:30]4=[N:31][C:32]([CH3:36])=[CH:33][C:34](=[O:35])[N:29]4[N:28]=2)[C@H:20]([NH:38][C:66](=[O:67])/[C:65](/[C:63]2[N:64]=[C:60]([NH:59][C:46]([C:40]4[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=4)([C:47]4[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=4)[C:53]4[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=4)[S:61][CH:62]=2)=[N:69]\[O:70][C:71]([O:74][CH3:75])([CH3:73])[CH3:72])[C:19]3=[O:39])=[O:16])[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 10868DicyclohexylcarbodiimideHCID 12833018(2Z)-2-(2-methoxypropan-2-yloxyimino)-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetic acidHCID 14124719(6R,7R)-7-amino-3-[(7-methyl-5-oxo-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-2-yl)thiomethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid diphenylmethyl ester

Product 1

HCID 16166545benzhydryl (6R,7R)-7-[[(2Z)-2-(2-methoxypropan-2-yloxyimino)-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-3-[(7-methyl-5-oxo-[1,3,4]thiadiazolo[3,2-a]pyrimidin-2-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateYield 41.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The product obtained in Step 2 (3.25 g) and 2-(2-triphenylmethylamino-4-thiazolyl)-2-[Z-(1-methoxy-1-methylethyl)oxyimino]acetic acid (5.64 g) were dissolved in dichloromethane (93 ml) and tetrahydrofuran (93 ml) under a nitrogen stream, and the solution was cooled to 0° C. Dicyclohexylcarbodiimide (2.32 g) was added to this solution by small portions, and the mixture was stirred overnight at room temperature. After filtering off the insoluble matters, the filtrate was concentrated under reduced pressure. The residue was redissolved in ethyl acetate and the insoluble matters were filtered off. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography, giving 2.5 g of the objective compound as yellow crystals.

Workup

  1. filtrationAfter filtering off the insoluble matters
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. dissolutionThe residue was redissolved in ethyl acetate
  4. filtrationthe insoluble matters were filtered off
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-10c01f667702495db7557981ff406a49
Source dataset
uspto-grants-1989_06
Patent number
US04840945

Reaction notes

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