O-(6-Chlorobenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium Tetrafluoroborate → tert-Butyl(+/-)-3-(3-(2-cyclopentyl-2-(4-((1,3-dioxoisoindolin-2-yl)methyl)phenyl)acetamido)-2-methylphenyl)propanoate

HRID 877225Notes

Reaction equation

HRID 877225 reaction equation
[CH:1]1([CH:6]([C:10]2[CH:15]=[CH:14][C:13]([CH2:16][N:17]3[C:25](=[O:26])[C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[C:18]3=[O:27])=[CH:12][CH:11]=2)[C:7](O)=[O:8])[CH2:5][CH2:4][CH2:3][CH2:2]1.[B-](F)(F)(F)F.CN(C(ON1N=NC2C=CC(Cl)=CC1=2)=[N+](C)C)C.[NH2:51][C:52]1[C:53]([CH3:67])=[C:54]([CH2:58][CH2:59][C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])[CH:55]=[CH:56][CH:57]=1>CN(C=O)C.N1C=CC=CC=1>[CH:1]1([CH:6]([C:10]2[CH:15]=[CH:14][C:13]([CH2:16][N:17]3[C:18](=[O:27])[C:19]4[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=4)[C:25]3=[O:26])=[CH:12][CH:11]=2)[C:7]([NH:51][C:52]2[C:53]([CH3:67])=[C:54]([CH2:58][CH2:59][C:60]([O:62][C:63]([CH3:64])([CH3:66])[CH3:65])=[O:61])[CH:55]=[CH:56][CH:57]=2)=[O:8])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 24898642O-(6-Chlorobenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium TetrafluoroborateHCID 58136304(+/-)-2-Cyclopentyl-2-(4-((1,3-dioxoisoindolin-2-yl)methyl)phenyl)acetic acidHCID 58136633Tert-butyl 3-(3-amino-2-methylphenyl)propanoate

Product 1

HCID 58136374tert-Butyl(+/-)-3-(3-(2-cyclopentyl-2-(4-((1,3-dioxoisoindolin-2-yl)methyl)phenyl)acetamido)-2-methylphenyl)propanoate

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6228DimethylformamideSolvent

Procedure

7.5 g (20.6 mmol) of (+/−)-2-cyclopentyl-2-(4-((1,3-dioxoisoindolin-2-yl)methyl)phenyl)acetic acid were dissolved in a mixture of 170 ml of DMF and 68 ml of pyridine, and 10.2 g (26.8 mmol) of TCTU were added. After 30 min of stirring at room temperature, 4.86 g (20.6 mmol) of tert-butyl 3-(3-amino-2-methylphenyl)propanoate were added. After stirring at room temperature overnight, the reaction mixture was concentrated and the residue pre-purified by flash chromatography on silica gel (mobile phase dichloromethane/methanol 100:1). The product obtained in this manner was triturated successively with ethanol and methanol, and the solid was filtered off with suction and dried under high vacuum. This gave 8.5 g (71% of theory) of the target compound.

Workup

  1. additionwere added
  2. stirringAfter stirring at room temperature overnight
  3. concentrationthe reaction mixture was concentrated
  4. customthe residue pre-purified by flash chromatography on silica gel (mobile phase dichloromethane/methanol 100:1)
  5. customThe product obtained in this manner
  6. customwas triturated successively with ethanol and methanol
  7. filtrationthe solid was filtered off with suction
  8. customdried under high vacuum

Sources & evidence

ORD record
ord-4f12e5a57f6f42608c1df17ea30a880a
Source dataset
uspto-grants-2015_03
Patent number
US08987256B2

Reaction notes

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