2-Pyridinecarboxaldehyde → (s)-1-(9h-Fluoren-9-yl)-14,14-dimethyl-3,12-dioxo-10-(pyridin-2-ylmethyl)-2,13-dioxa-4,10-diazapentadecane-5-carboxylic acid

HRID 1043369노트

반응식

HRID 1043369 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.[N:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[CH:35]=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[C:51]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])(=[O:54])[CH:52]=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]([CH2:35][C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][N:29]=3)[CH2:52][C:51](=[O:54])[O:55][C:56]([CH3:59])([CH3:58])[CH3:57])[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 142732-PyridinecarboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 10986247Tert-butyl 2-oxoacetateHCID 11858928(2S)-6-amino-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)hexanoic acid hydrochloride

생성물 1

HCID 59408713(s)-1-(9h-Fluoren-9-yl)-14,14-dimethyl-3,12-dioxo-10-(pyridin-2-ylmethyl)-2,13-dioxa-4,10-diazapentadecane-5-carboxylic acid수율 28%

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 (4.859 g, 12 mmol) and 2-pyridinecarboxaldehyde (1.285 g, 12 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 (6.36 g, 30 mmol) and crude tert-butyl glyoxalate (2.34 g, 18 mmol) 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-(pyridin-2-ylmethyl)-2,13-dioxa-4,10-diazapentadecane-5-carboxylic acid (1.924 g, 28%). 1H NMR (400 MHz, CDCl3) 8.89 (d, J=4.4 Hz, 1H), 8.06 (d, J=8.0 Hz, 1H), 8.02 (d, J=7.6 Hz, 2H), 7.88 (t, J=5.8 Hz, 2H), 7.81 (d, J=7.6 Hz, 1H), 7.66 (t, J=7.4 Hz, 2H), 7.60-7.53 (m, 4H), 6.03 (d, J=7.2 Hz, 1H), 4.67-4.22 (m, 8H), 3.64-3.53 (m, 2H), 3.12 (t, J=6.8 Hz, 2H), 2.19-2.08 (m, 2H), 1.92-1.79 (m, 2H), 1.73 (s, 9H); MS (ESI), 564 (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-2a1739e315884df68fefcfe49b9c9b6c
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08562945B2

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