4-Bromobutyronitrile → 3-[2(R)-{3-cyanopropyl-amino}-2-phenylethyl]-5-(2-fluoro-3-methoxyphenyl)-1-[2-fluoro-6-(trifluoromethyl)benzyl]-6-methyl-pyrimidine-2,4(1H,3H)-dione

HRID 28499

Reaction equation

HRID 28499 reaction equation
[NH2:1][C@H:2]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[CH2:3][N:4]1[C:9](=[O:10])[C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH3:18])[C:12]=2[F:19])=[C:7]([CH3:20])[N:6]([CH2:21][C:22]2[C:27]([C:28]([F:31])([F:30])[F:29])=[CH:26][CH:25]=[CH:24][C:23]=2[F:32])[C:5]1=[O:33].C(N(C(C)C)CC)(C)C.Br[CH2:50][CH2:51][CH2:52][C:53]#[N:54]>C(#N)C>[C:53]([CH2:52][CH2:51][CH2:50][NH:1][C@H:2]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[CH2:3][N:4]1[C:9](=[O:10])[C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH3:18])[C:12]=2[F:19])=[C:7]([CH3:20])[N:6]([CH2:21][C:22]2[C:27]([C:28]([F:29])([F:31])[F:30])=[CH:26][CH:25]=[CH:24][C:23]=2[F:32])[C:5]1=[O:33])#[N:54]

Participants

5

Reactant 3

HCID 214124-BromobutyronitrileHCID 81531DiisopropylethylamineHCID 114214123-((R)-2-Amino-2-phenylethyl)-5-(2-fluoro-3-methoxyphenyl)-1-(2-fluoro-6-trifluoromethylbenzyl)-6-methyl-1H-pyrimidine-2,4-dione

Product 1

HCID 691894153-[2(R)-{3-cyanopropyl-amino}-2-phenylethyl]-5-(2-fluoro-3-methoxyphenyl)-1-[2-fluoro-6-(trifluoromethyl)benzyl]-6-methyl-pyrimidine-2,4(1H,3H)-dioneYield 94%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Compound 1f (110 mg, 0.2 mmol) was dissolved in acetonitrile (5 mL) and diisopropylethyl amine (52 mg, 0.4 mmol) was added, followed by the addition of 4-bromobutyronitrile (90 mg, 0.6 mmol). The reaction mixture was refluxed for 16 hours. Volatiles were evaporated and the residue was purified by flash chromatography (silica, 5% MeOH/CH2Cl2) to give compound 3a (115 mg, 94%). MS (CI) m/z 613.3 (MH+).

Workup

  1. temperatureThe reaction mixture was refluxed for 16 hours
  2. customVolatiles were evaporated
  3. customthe residue was purified by flash chromatography (silica, 5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-b86f9762f7644a4dbb9725fb0521d333
Source dataset
uspto-grants-2008_09
Patent number
US07419983B2

Linked notes

Loading…