Diisopropylethylamine → 3-(tert-butyldimethylsilyloxy)-N-((5-chloro-2-methoxyphenyl)(cyano)methyl)-3-methylbutanamide

HRID 1466669Notes

Reaction equation

HRID 1466669 reaction equation
[NH2:1][CH:2]([C:5]1[CH:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:6]=1[O:12][CH3:13])[C:3]#[N:4].[C:14]([Si:18]([CH3:28])([CH3:27])[O:19][C:20]([CH3:26])([CH3:25])[CH2:21][C:22](O)=[O:23])([CH3:17])([CH3:16])[CH3:15].C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(OCC)(=O)C>[Si:18]([O:19][C:20]([CH3:26])([CH3:25])[CH2:21][C:22]([NH:1][CH:2]([C:5]1[CH:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:6]=1[O:12][CH3:13])[C:3]#[N:4])=[O:23])([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:28])[CH3:27]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66847023Amino-(5-chloro-2-methoxy-phenyl)-acetonitrileHCID 866418543-(tert-Butyldimethylsilyloxy)-3-methylbutyric acid

Product 1

HCID 668471763-(tert-butyldimethylsilyloxy)-N-((5-chloro-2-methoxyphenyl)(cyano)methyl)-3-methylbutanamideYield 73%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

2-amino-2-(5-chloro-2-methoxyphenyl)acetonitrile (500 mg, 2.54 mmol) in DMF (2 mL) was added to a solution of 3-(tert-butyl-dimethyl-silanyloxy)-3-methyl-butyric acid (prepared according to patent EP2025667) (590 mg, 2.54 mmol), diisopropylethylamine (0.87 mL, 5.08 mmol) and HATU (966 mg, 2.54 mmol) in DMF (5 mL) and stirred for 18 hours. Ethyl acetate was added, the organics washed with sodium hydrogen carbonate (sat. aq.) and brine, then evaporated to dryness. The residues were purified by flash chromatography on silica gel (0 to 5% ethyl acetate in dichloromethane) to yield 740 mg (73%) of 3-(tert-butyldimethylsilyloxy)-N-((5-chloro-2-methoxyphenyl)(cyano)methyl)-3-methylbutanamide. LCMS (ESI) m+H=411.4.

Workup

  1. washthe organics washed with sodium hydrogen carbonate (sat. aq.) and brine
  2. customevaporated to dryness
  3. customThe residues were purified by flash chromatography on silica gel (0 to 5% ethyl acetate in dichloromethane)

Sources & evidence

ORD record
ord-ef0bf94875b54c73a42470b5a131940d
Source dataset
uspto-grants-2015_04
Patent number
US08999998B2

Reaction notes

Loading…