1,3-Thiazole-2-carbaldehyde → (S)-1-(9H-fluoren-9-yl)-14,14-dimethyl-3,12-dioxo-10-(thiazol-2-ylmethyl)-2,13-dioxa-4,10-diazapentadecane-5-carboxylic acid

HRID 56315노트

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HRID 56315 반응식
[NH:1]([C:11]([O:13][CH2:14][CH:15]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:21]2[C:16]1=[CH:17][CH:18]=[CH:19][CH:20]=2)=[O:12])[C@H:2]([C:8]([OH:10])=[O:9])[CH2:3][CH2:4][CH2:5][CH2:6][NH2:7].Cl.[S:29]1[CH:33]=[CH:32][N:31]=[C:30]1[CH:34]=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[C:50]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])(=[O:53])[CH:51]=O>ClCCCl.O>[CH:17]1[C:16]2[CH:15]([CH2:14][O:13][C:11](=[O:12])[NH:1][C@H:2]([C:8]([OH:10])=[O:9])[CH2:3][CH2:4][CH2:5][CH2:6][N:7]([CH2:34][C:30]3[S:29][CH:33]=[CH:32][N:31]=3)[CH2:51][C:50](=[O:53])[O:54][C:55]([CH3:58])([CH3:57])[CH3:56])[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:21]=2[CH:20]=[CH:19][CH:18]=1

참가 물질

7

반응물 4

HCID 27349031,3-Thiazole-2-carbaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 10986247Tert-butyl 2-oxoacetateHCID 11858928(2S)-6-amino-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)hexanoic acid hydrochloride

생성물 1

HCID 59408631(S)-1-(9H-fluoren-9-yl)-14,14-dimethyl-3,12-dioxo-10-(thiazol-2-ylmethyl)-2,13-dioxa-4,10-diazapentadecane-5-carboxylic acid수율 21.3%

시약·촉매·용매 2

HCID 111,2-Dichloroethane용매HCID 962Water용매

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온도
0 °C

실험 절차

A suspension of Fmoc-Lys-OH.HCl (6.07 g, 15 mmol) and thiazole-2-carbaldehyde (1.697 g, 15 mmol) in DCE (100 mL) was refluxed for 30 min under nitrogen. The reaction mixture was cooled to 0° C., and treated sequentially with NaBH(OAc)3 (7.95 g, 37.5 mmol) and crude tert-butyl glyoxalate (3.53 g). The reaction mixture was stirred at room temperature for overnight and decomposed with water. The reaction mixture was extracted with DCM. The organic layer was dried and concentrated under reduced pressure. The residue was purified by flash chromatography over silica gel to afford (S)-1-(9H-fluoren-9-yl)-14,14-dimethyl-3,12-dioxo-10-(thiazol-2-ylmethyl)-2,13-dioxa-4,10-diazapentadecane-5-carboxylic acid (1.85 g, 21%). MS (ESI), 580 (M+H)+.

후처리

  1. temperaturewas refluxed for 30 min under nitrogen
  2. extractionThe reaction mixture was extracted with DCM
  3. customThe organic layer was dried
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by flash chromatography over silica gel

출처 및 근거

ORD 기록
ord-e9f775bff2744e18bab9666cd4bccb02
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09433594B2

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