Dimethylformamide → HCID 86732850, compound

HRID 2392361Notes

Reaction equation

HRID 2392361 reaction equation
C[NH:2][C:3](N[C@H](C(O)=O)C(C)C)=[O:4].CN(C(ON1N=NC2[CH:24]=[CH:25][CH:26]=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:37]([N:40]([CH:43]([CH3:45])C)[CH2:41][CH3:42])([CH3:39])C.[C:46]([O:50][C:51]([N:53]1CCNC(C(O)=O)C1)=[O:52])([CH3:49])([CH3:48])[CH3:47].Cl.NC[C:65](C1C=CC(Br)=CC=1)=[O:66].CN(C=[O:78])C>>[C:46]([O:50][C:51]([N:53]1[CH2:42][CH2:41][N:40]([C:37](=[O:78])[CH:39]([NH:2][C:3]([O:66][CH3:65])=[O:4])[CH:25]([CH3:24])[CH3:26])[CH2:43][CH2:45]1)=[O:52])([CH3:47])([CH3:48])[CH3:49]

Participants

7

Reactant 6

HCID 6228Dimethylformamide2×HCID 81531Diisopropylethylamine3×HCID 27982162-Amino-1-(4-bromophenyl)ethan-1-one hydrochlorideHCID 51758554-[(Tert-butoxy)carbonyl]piperazine-2-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 30077188N-[(Methylamino)carbonyl]-L-valine

Product 1

HCID 86732850HCID 86732850, compound

Procedure

N-(Methylcarbamoyl)(L)-valine (2.0 g, 11.4 mmol) was dissolved in DMF (15 mL) at room temperature. HATU (4.34 g, 11.4 mmol) and diisopropyl ethylamine (1.47 g, 11.4 mmol) were added and stirring was continued. After 10 minutes, solid piperazine-1,3-dicarboxylic acid 1-tert-butyl ester (2.62 g, 11.4 mmol) was added. To the resultant suspension was added DMF (10 mL) and diisopropyl ethylamine (1.47 g, 11.4 mmol). Stirring at room temperature was continued. After 45 min, HATU (4.34 g, 11.4 mmol) and diisopropyl ethylamine (1.47 g, 11.4 mmol) were added to the resultant yellow solution followed by amino-(4′bromo) acetophenone hydrochloride salt (2.85 g, 11.4 mmol). After 30 minutes all volatiles were removed in vacuo. The crude material was taken into EtOAc and the organic layer was washed with aqueous HCl (1 M), aqueous LiCl (5%), aqueous bicarbonate solution, brine and was dried over sodium sulfate. Filtration and evaporation of solvents in vacuo yielded crude material, which was purified by flash chromatography on silica gel (eluent: EtOAc w MeOH 10%/hexanes) to yield the product 342-(4-Bromo-phenyl)-2-oxo-ethylcarbamoyl]-4-(2-methoxycarbonylamino-3-methyl-butyryl)-piperazine-1-carboxylic acid tert-butyl ester (3.62 g): LCMS-ESI+: calc'd for C25H35BrN4O7: 583.4 (M+). Found: 583.2 /585.2 (M+H+).

Workup

  1. stirringStirring at room temperature
  2. waitAfter 45 min
  3. customAfter 30 minutes all volatiles were removed in vacuo
  4. washthe organic layer was washed with aqueous HCl (1 M), aqueous LiCl (5%), aqueous bicarbonate solution, brine
  5. dry with materialwas dried over sodium sulfate
  6. filtrationFiltration and evaporation of solvents in vacuo
  7. customyielded crude material, which
  8. customwas purified by flash chromatography on silica gel (eluent: EtOAc w MeOH 10%/hexanes)

Sources & evidence

ORD record
ord-be074de7b81042109ca552d90f45324b
Source dataset
uspto-grants-2012_09
Patent number
US08273341B2

Reaction notes

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