Dicyclohexylcarbodiimide → (9H-fluoren-9-yl)methyl ((S)-3-methyl-1-oxo-1-(((S)-1-oxo-1-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)amino)propan-2-yl)amino)butan-2-yl)carbamate

HRID 1482765Notes

Reaction equation

HRID 1482765 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([B:8]2[O:16][C:13]([CH3:15])([CH3:14])[C:10]([CH3:12])([CH3:11])[O:9]2)=[CH:4][CH:3]=1.[CH:17]1[C:29]2[CH:28]([CH2:30][O:31][C:32]([NH:34][C@H:35]([CH:44]([CH3:46])[CH3:45])[C:36]([NH:38][C@H:39]([CH3:43])[C:40](O)=[O:41])=[O:37])=[O:33])[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:21]=2[CH:20]=[CH:19][CH:18]=1.C1CCC(N=C=NC2CCCCC2)CC1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH3:45][CH:44]([CH3:46])[C@H:35]([NH:34][C:32](=[O:33])[O:31][CH2:30][CH:28]1[C:27]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[C:21]2[C:29]1=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:36](=[O:37])[NH:38][C@@H:39]([CH3:43])[C:40](=[O:41])[NH:1][C:2]1[CH:7]=[CH:6][C:5]([B:8]2[O:16][C:13]([CH3:15])([CH3:14])[C:10]([CH3:11])([CH3:12])[O:9]2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 27346204-(Tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 67451920(2R)-2-[(2R)-2-({[(9H-fluoren-9-yl)methoxy]carbonyl}amino)-3-methylbutanamido]propanoic acid

Product 1

HCID 90247031(9H-fluoren-9-yl)methyl ((S)-3-methyl-1-oxo-1-(((S)-1-oxo-1-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)amino)propan-2-yl)amino)butan-2-yl)carbamateYield 88%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

4-Aminophenylboronic acid pinacol ester was added (146.9 mg, 0.67 mmol) was added to a solution of HO-Ala-Val-Fmoc 20b (330 mg, 0.8 mmol), DCC (166 mg, 0.8 mmol) and DMAP (5 mg, cat.) in dry DCM (8 mL) previously stirred for 30 minutes at room temperature in a flask flushed with argon. The reaction mixture was then allowed to stir at room temperature overnight. The reaction was followed by LCMS and TLC. The reaction mixture was diluted with CH2Cl2 and the organics were washed with H2O and brine before being dried with MgSO4, filtered and the solvent removed by rotary evaporation under reduced pressure. The crude product was dryloaded on a silicagel chromatography column (Hexane/EtOAc, 6:4) and pure product 20 was isolated as a white solid in 88% yield (360 mg).

Workup

  1. customflushed with argon
  2. stirringto stir at room temperature overnight
  3. additionThe reaction mixture was diluted with CH2Cl2
  4. washthe organics were washed with H2O and brine
  5. dry with materialbefore being dried with MgSO4
  6. filtrationfiltered
  7. customthe solvent removed by rotary evaporation under reduced pressure

Sources & evidence

ORD record
ord-318df13f6182490e87754a66ed14e556
Source dataset
uspto-grants-2016_08
Patent number
US09415117B2

Reaction notes

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