Diisopropylethylamine → HCID 178462286, compound

HRID 584094Notes

Reaction equation

HRID 584094 reaction equation
C(O)(=O)C.NN.C([S:10][C@@H:11]1[CH2:15][N:14]([CH3:16])[C@H:13]([C:17]([N:19]2[CH2:23][CH2:22][C@H:21]([NH:24][C:25](=[O:57])[CH2:26][NH:27][C:28]([NH:43][C:44]([O:46][CH2:47][C:48]3[CH:53]=[CH:52][C:51]([N+:54]([O-:56])=[O:55])=[CH:50][CH:49]=3)=[O:45])=[N:29][C:30]([O:32][CH2:33][C:34]3[CH:39]=[CH:38][C:37]([N+:40]([O-:42])=[O:41])=[CH:36][CH:35]=3)=[O:31])[CH2:20]2)=[O:18])[CH2:12]1)(=O)C.[OH:58][C@@H:59]([C@H:61]1[C:96](=[O:97])[N:63]2[C:64]([C:83]([O:85][CH2:86][C:87]3[CH:92]=[CH:91][C:90]([N+:93]([O-:95])=[O:94])=[CH:89][CH:88]=3)=[O:84])=[C:65](OP(C3C=CC=CC=3)(C3C=CC=CC=3)=O)[C@H:66]([CH3:67])[C@H:62]12)[CH3:60].C(N(CC)C(C)C)(C)C.C(=O)([O-])O.[Na+]>CN(C)C=O.O1CCCC1>[N+:40]([C:37]1[CH:38]=[CH:39][C:34]([CH2:33][O:32][C:30]([N:29]=[C:28]([NH:43][C:44]([O:46][CH2:47][C:48]2[CH:53]=[CH:52][C:51]([N+:54]([O-:56])=[O:55])=[CH:50][CH:49]=2)=[O:45])[NH:27][CH2:26][C:25]([NH:24][C@H:21]2[CH2:22][CH2:23][N:19]([C:17]([C@@H:13]3[CH2:12][C@H:11]([S:10][C:65]4[C@H:66]([CH3:67])[C@@H:62]5[C@@H:61]([C@H:59]([OH:58])[CH3:60])[C:96](=[O:97])[N:63]5[C:64]=4[C:83]([O:85][CH2:86][C:87]4[CH:88]=[CH:89][C:90]([N+:93]([O-:95])=[O:94])=[CH:91][CH:92]=4)=[O:84])[CH2:15][N:14]3[CH3:16])=[O:18])[CH2:20]2)=[O:57])=[O:31])=[CH:35][CH:36]=1)([O-:42])=[O:41]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 165591Hydrazine, acetate (1:1)HCID 516892Sodium BicarbonateHCID 15871605p-nitrobenzyl (1R,5R,6S)-2-(di-phenylphosphoryloxy)-6-[(R)-1-hydroxyethyl]-1-methyl-carbapen-2-em-3-carboxylateHCID 178477149HCID 178477149, compound

Product 1

HCID 178462286HCID 178462286, compoundYield 66.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

Hydrazine acetate (652 mg) was added to a solution of (2S,4S)-4-acetylthio-2-[(3S)-3-[2-[2,3-bis(4-nitrobenzyloxycarbonyl)guanidino]acetylamino]pyrrolidin-1-ylcarbonyl]-1-methylpyrrolidine (4.3 g) in N,N-dimethylformamide (86 ml) and stirred at room temperature for 4 hours. To the resulting mixture was added 4-nitrobenzyl (1R,5R,6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-diphenylphosphoryloxy-1-carbapen-2-em-3-carboxylate (3.53 g) and N,N-diisopropylethylamine (1.34 ml) and allowed to react at −30° C. for 3 days. At the end of this time, to the reaction mixture was added 1% aqueous sodium hydrogencarbonate solution and the resulting precipitate was filtered, washed with water, and dissolved in a mixture of tetrahydrofuran and ethyl acetate (3:7). The resulting solution was washed successively with saturated aqueous sodium hydrogencarbonate solution, water and saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated in vacuo. The resulting residue was chromatographed on a silica gel column using 10% methanol/ethyl acetate and 20% methanol/ethyl acetate as the eluant to afford the crude desired product. The product was dissolved in tetrahydrofuran and reprecipitated with a mixture of ethyl acetate and ether (1:1) to give the desired compound (4.02 g) as a pale yellow powder.

Workup

  1. customto react at −30° C. for 3 days
  2. filtrationthe resulting precipitate was filtered
  3. washwashed with water
  4. dissolutiondissolved in a mixture of tetrahydrofuran and ethyl acetate (3:7)
  5. washThe resulting solution was washed successively with saturated aqueous sodium hydrogencarbonate solution, water and saturated aqueous sodium chloride solution
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe resulting residue was chromatographed on a silica gel column
  9. customto afford the crude desired product
  10. customreprecipitated with a mixture of ethyl acetate and ether (1:1)

Sources & evidence

ORD record
ord-1ea670dc14044f8dbd0e357677c92c1a
Source dataset
uspto-grants-2005_08
Patent number
US06924279B2

Reaction notes

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