Diisopropylethylamine → p-nitrobenzyl (1R,5S,6S)-2-{1-[4-((1S)-1-carbamoyl-2-methyl-propylcarbamoyl)-1,3-thiazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-t-butyldimethylsilyloxyethyl]-1-methylcarbapen-2-em-3-carboxylate

HRID 891701노트

반응식

HRID 891701 반응식
[C:1]([C:4]1[N:5]=[C:6]([N:9]2[CH2:12][CH:11]([S:13][C:14]3[C@H:15]([CH3:45])[C@@H:16]4[C@@H:33]([C@H:34]([O:36][Si:37]([C:40]([CH3:43])([CH3:42])[CH3:41])([CH3:39])[CH3:38])[CH3:35])[C:32](=[O:44])[N:17]4[C:18]=3[C:19]([O:21][CH2:22][C:23]3[CH:28]=[CH:27][C:26]([N+:29]([O-:31])=[O:30])=[CH:25][CH:24]=3)=[O:20])[CH2:10]2)[S:7][CH:8]=1)(O)=[O:2].Cl.[NH2:47][C@H:48]([C:52]([NH2:54])=[O:53])[CH:49]([CH3:51])[CH3:50].C(P(C#N)(CC)=O)C.C(N(C(C)C)CC)(C)C>CN(C)C=O>[C:52]([C@@H:48]([NH:47][C:1]([C:4]1[N:5]=[C:6]([N:9]2[CH2:10][CH:11]([S:13][C:14]3[C@H:15]([CH3:45])[C@@H:16]4[C@@H:33]([C@H:34]([O:36][Si:37]([C:40]([CH3:41])([CH3:42])[CH3:43])([CH3:39])[CH3:38])[CH3:35])[C:32](=[O:44])[N:17]4[C:18]=3[C:19]([O:21][CH2:22][C:23]3[CH:24]=[CH:25][C:26]([N+:29]([O-:31])=[O:30])=[CH:27][CH:28]=3)=[O:20])[CH2:12]2)[S:7][CH:8]=1)=[O:2])[CH:49]([CH3:51])[CH3:50])(=[O:53])[NH2:54]

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 13586794DiethylphosphorylcyanideHCID 13689583L-Valinamide--hydrogen chloride (1/1)HCID 131725364p-nitrobenzyl (1R,5S,6S)-2-[1-(4-carboxy-1,3-thiazol-2-yl)azetidin-3-yl]thio-6-[(R)-1-t-butyldimethylsilyloxyethyl]-1-methyl-carbapen-2-em-3-carboxylate

생성물 1

HCID 131725332p-nitrobenzyl (1R,5S,6S)-2-{1-[4-((1S)-1-carbamoyl-2-methyl-propylcarbamoyl)-1,3-thiazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-t-butyldimethylsilyloxyethyl]-1-methylcarbapen-2-em-3-carboxylate수율 82%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of p-nitrobenzyl (1R,5S,6S)-2-[1-(4-carboxy-1,3-thiazol-2-yl)azetidin-3-yl]thio-6-[(R)-1-t-butyldimethylsilyloxyethyl]-1-methylcarbapen-2-em-3-carboxylate (1.00 g, 1.48 mmol) (obtained as described in Reference Example 41(7)) and L-valinamide hydrochloride (272 mg, 1.78 mmol) obtained as described in Reference Example 47(2) in dimethylformamide (50 ml) were added diethylphosphoryl cyanide (275 μl, 1.78 mmol) and diisopropylethylamine (620 μl, 3.56 mmol) in an ice bath under an atmosphere of nitrogen. The mixture was stirred at room temperature for 2.5 hours. After checking the completion of the reaction, the reaction mixture was partitioned between ethyl acetate and 10% aqueous sodium chloride solution. The obtained organic layer was washed successively with saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column using n-hexane:ethyl acetate (1:3)→methylene chloride:ethyl acetate (3:1) as the eluant to afford p-nitrobenzyl (1R,5S,6S)-2-{1-[4-((1S)-1-carbamoyl-2-methylpropylcarbamoyl)-1,3-thiazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-t-butyldimethylsilyloxyethyl]-1-methylcarbapen-2-em-3-carboxylate (934 mg, yield 82%).

후처리

  1. customthe completion of the reaction
  2. customthe reaction mixture was partitioned between ethyl acetate and 10% aqueous sodium chloride solution
  3. washThe obtained organic layer was washed successively with saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by chromatography on a silica gel column

출처 및 근거

ORD 기록
ord-c370ed97b89b4efda838ae07536a52ce
출처 데이터셋
uspto-grants-2006_02
특허 번호
US07001897B2

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