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 56315Notes

Reaction equation

HRID 56315 reaction equation
[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

Participants

7

Reactant 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

Product 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 acidYield 21.3%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

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)+.

Workup

  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

Sources & evidence

ORD record
ord-e9f775bff2744e18bab9666cd4bccb02
Source dataset
uspto-grants-2016_09
Patent number
US09433594B2

Reaction notes

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