4-Methylmorpholine → 2-[2-({[2-(4-Bromo-phenyl)-2-oxo-ethyl carbamoyl]-methyl}-tert-butoxycarbonyl-amino)-acetylamino]-3-methyl-butyric acid methyl ester

HRID 71759

Reaction equation

HRID 71759 reaction equation
CN1CCOCC1.[Br:8][C:9]1[CH:14]=[CH:13][C:12]([C:15](=[O:33])[CH2:16][NH:17][C:18]([CH2:20][N:21]([CH2:29][C:30](O)=[O:31])[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[O:19])=[CH:11][CH:10]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[CH3:59][O:60][C:61](=[O:67])[C@@H:62]([CH:64]([CH3:66])[CH3:65])[NH2:63]>CN(C)C=O>[CH3:59][O:60][C:61](=[O:67])[CH:62]([NH:63][C:30](=[O:31])[CH2:29][N:21]([CH2:20][C:18](=[O:19])[NH:17][CH2:16][C:15]([C:12]1[CH:13]=[CH:14][C:9]([Br:8])=[CH:10][CH:11]=1)=[O:33])[C:22]([O:24][C:25]([CH3:27])([CH3:28])[CH3:26])=[O:23])[CH:64]([CH3:66])[CH3:65]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11984198Methyl D-valinate hydrochlorideHCID 59611182({[2-(4-Bromo-phenyl)-2-oxo-ethylcarbamoyl]-methyl}-tert-butoxycarbonyl-amino)-acetic acid

Product 1

HCID 666202862-[2-({[2-(4-Bromo-phenyl)-2-oxo-ethyl carbamoyl]-methyl}-tert-butoxycarbonyl-amino)-acetylamino]-3-methyl-butyric acid methyl esterYield 87.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-Methylmorpholine (4.1 mL, 37.3 mmol) was added to a suspension of ({[2-(4-bromo-phenyl)-2-oxo-ethylcarbamoyl]-methyl}-tert-butoxycarbonyl-amino)-acetic acid (4 g, 9.3 mmol), and HATU (4.61 g, 12.1 mmol) in dimethylformamide (25 mL). After 5 minutes d-valine methyl ester hydrochloride (1.56 g, 9.3 mmol), was added to the solution. After 1 hour the solvent was removed under reduced pressure. The residue was taken up in ethyl acetate (150 mL), and washed with water (100 mL), aqueous hydrogen chloride (0.5 N, 2×100 mL), saturated sodium bicarbonate (100 mL), and saturated sodium chloride (100 mL). The organic phase was dried over sodium sulfate, filtered and the solvent was removed under reduced pressure. The residue was subjected to flash chromatography with eluent of (10% methanol in ethyl acetate) and hexane. The product-containing fractions were combined and the solvent was removed under reduced pressure to yield 2-[2-({[2-(4-bromo-phenyl)-2-oxo-ethylcarbamoyl]-methyl}-tert-butoxycarbonyl-amino)-acetylamino]-3-methyl-butyric acid methyl ester (4.37 g, 8.1 mmol, 87%). C23H32BrN3O7 calculated 541.1 observed [M+1]+ 431.1; rt=2.65 min.

Workup

  1. additionwas added to the solution
  2. customAfter 1 hour the solvent was removed under reduced pressure
  3. washwashed with water (100 mL), aqueous hydrogen chloride (0.5 N, 2×100 mL), saturated sodium bicarbonate (100 mL), and saturated sodium chloride (100 mL)
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. filtrationfiltered
  6. customthe solvent was removed under reduced pressure
  7. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-906095a9bdb344c29da5ab6380b551bd
Source dataset
uspto-grants-2014_09
Patent number
US08822430B2

Linked notes

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