Trifluoroacetic acid → HCID 57497158, compound

HRID 2409126Notes

Reaction equation

HRID 2409126 reaction equation
C(OC(=O)[NH:7][C:8]1[N:9]([CH3:26])[C:10](=[O:25])[C:11]([CH3:24])([CH3:23])[C@:12]([C:15]2[CH:20]=[C:19]([Br:21])[CH:18]=[CH:17][C:16]=2[F:22])([CH3:14])[N:13]=1)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[NH2:7][C:8]1[N:9]([CH3:26])[C:10](=[O:25])[C:11]([CH3:23])([CH3:24])[C@:12]([C:15]2[CH:20]=[C:19]([Br:21])[CH:18]=[CH:17][C:16]=2[F:22])([CH3:14])[N:13]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 57497154[(S)-4-(5-bromo-2-fluoro-phenyl)-1,4,5,5-tetramethyl-6-oxo-1,4,5,6-tetrahydro-pyrimidin-2-yl]-carbamic acid tert-butyl ester2×

Product 1

HCID 57497158HCID 57497158, compoundYield 99.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of [(S)-4-(5-bromo-2-fluoro-phenyl)-1,4,5,5-tetramethyl-6-oxo-1,4,5,6-tetrahydro-pyrimidin-2-yl]-carbamic acid tert-butyl ester (intermediate E8, 7.0 g) in dichloromethane (100 ml) was added trifluoroacetic acid (36.3 ml) and stirring was continued at 22° C. for 4 h. The mixture was evaporated and the residue partitioned between saturated aqueous NaHCO3 and dichloromethane, the organic layer was dried and evaporated and the residue triturated with n-pentane to give the intermediate (S)-2-amino-6-(5-bromo-2-fluoro-phenyl)-3,5,5,6-tetramethyl-5,6-dihydro-3H-pyrimidin-4-one (5.4 g) as a white solid. To a solution of the intermediate (0.88 g) in dichloromethane (13 ml) was added 4,4′-dimethoxytrityl chloride (0.96 g) and triethylamine (0.52 g) and stirring was continued at 22° C. for 2 h. The solution was washed with water, the organic layer was dried, evaporated and the residue was purified by chromatography over silica using AcOEt/n-heptane, gradient from 0 to 20% AcOEt) to give (S)-2-{[bis-(4-methoxy-phenyl)-phenyl-methyl]-amino}-6-(5-bromo-2-fluoro-phenyl)-3,5,5,6-tetramethyl-5,6-dihydro-3H-pyrimidin-4-one as (1.61 g) as a pale blue solid. MS (ESI): m/z=642.3 and 644.3 [M+H]+.

Workup

  1. customThe mixture was evaporated
  2. customthe residue partitioned between saturated aqueous NaHCO3 and dichloromethane
  3. customthe organic layer was dried
  4. customevaporated
  5. customthe residue triturated with n-pentane

Sources & evidence

ORD record
ord-33ddad0143b543dbba8e3df1a71955f4
Source dataset
uspto-grants-2014_08
Patent number
US08815881B2

Reaction notes

Loading…