Methyl iodide → (S)-4-(3-Methyl-2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-2,3,4,5,6,7-hexahydro-1H-cyclopenta[d]pyrimidin-4-yl)-3-(methylsulfonyl)benzonitrile

HRID 927239Notes

Reaction equation

HRID 927239 reaction equation
[O:1]=[C:2]1[N:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=2)[C:6]2[CH2:18][CH2:19][C:20](=[O:21])[C:5]=2[C@@H:4]([C:22]2[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[CH:24][C:23]=2[S:30]([CH3:33])(=[O:32])=[O:31])[NH:3]1.[CH:34]([N-]C(C)C)(C)C.[Li+].CI>CN(C)C=O.C(#N)C>[CH3:34][N:3]1[C@H:4]([C:22]2[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[CH:24][C:23]=2[S:30]([CH3:33])(=[O:31])=[O:32])[C:5]2[C:20](=[O:21])[CH2:19][CH2:18][C:6]=2[N:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:15])[F:16])[CH:9]=2)[C:2]1=[O:1]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 2724682Lithium diisopropylamideHCID 77844826(S)-4-(2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-2,3,4,5,6,7-hexahydro-1H-cyclopenta[d]-pyrimidin-4-yl)-3-(methylsulfonyl)benzonitrile

Product 1

HCID 77844884(S)-4-(3-Methyl-2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-2,3,4,5,6,7-hexahydro-1H-cyclopenta[d]pyrimidin-4-yl)-3-(methylsulfonyl)benzonitrile

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

A solution of (S)-4-(2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-2,3,4,5,6,7-hexahydro-1H-cyclopenta[d]pyrimidin-4-yl)-3-(methylsulfonyl)benzonitrile (example 10A, 50 mg, 0.11 mmol) in N,N-dimethylformamide (1.0 mL) is treated with lithium diisopropylamide (1.8 M in tetrahydrofuran/heptane/ethylbenzene, 63 μL, 0.12 mmol) and methyl iodide (9 μL, 0.14 mmol). After 20 min the mixture is diluted with acetonitrile and purified by reversed phase HPLC (Agilent ZORBAX™ SB-C18, gradient of acetonitrile in water, 0.1% formic acid). Yield: 15 mg; ESI mass spectrum [M+H]+=490; Retention time HPLC: 1.00 min (Z017_S04).

Workup

  1. custompurified by reversed phase HPLC (Agilent ZORBAX™ SB-C18, gradient of acetonitrile in water, 0.1% formic acid)
  2. custom1.00 min (Z017_S04)

Sources & evidence

ORD record
ord-4eb2e594195d48c79503bdfbde87484b
Source dataset
uspto-grants-2016_03
Patent number
US09290459B1

Reaction notes

Loading…