Sodium bis(trimethylsilyl)amide → 4-[2-(2,2-Dimethyl-5-oxopyrrolidin-1-yl)-1,3-thiazol-4-yl]benzonitrile

HRID 1436433Notes

Reaction equation

[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11]([NH:14][C:15]([CH3:23])([CH3:22])[CH2:16][CH2:17][C:18](OC)=[O:19])[S:12][CH:13]=2)=[CH:5][CH:4]=1)#[N:2].C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>O1CCCC1>[CH3:22][C:15]1([CH3:23])[CH2:16][CH2:17][C:18](=[O:19])[N:14]1[C:11]1[S:12][CH:13]=[C:9]([C:6]2[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[CH:4][CH:5]=2)[N:10]=1

Participants

Conditions

Temperature: 25 °C

Procedure

Methyl 4-{[4-(4-cyanophenyl)-1,3-thiazol-2-yl]amino}-4-methylpentanoate (0.31 g, 0.94 mmol), prepared in the previous step, was dissolved in tetrahydrofuran (18 mL) and sodium bis(trimethylsilyl)amide (1M in tetrahydrofuran, 0.94 mL, 0.94 mmol) was added. The mixture was stirred at 25° C. for 2 h. The reaction was quenched with saturated NH4Cl, diluted with ethyl acetate, washed with H2O, brine, dried over anhydrous MgSO4, filtered and concentrated. Flash chromatography (20% acetone/hexane) afforded the title compound (0.27 g, 97%) as a white solid. HRMS: calcd for C16H15N3OS+H+, 298.10086; found (ESI, [M+H]+), 298.1; Analytical HPLC: purity 94.8% at 210-370 nm, 9.9 min; 98.2% at 244 nm, 9.9 min; the Xterra® RP18 column, 3.5%, 150×4.6 mm column, 1.2 mL/min, 85/15-5/95 (Ammon. Form. Buff. pH=3.5/ACN+MeOH) for 10 min, hold 4 min.

Workup

customThe reaction was quenched with saturated NH4Cl
additiondiluted with ethyl acetate
washwashed with H2O, brine
dry with materialdried over anhydrous MgSO4
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-52f914fa57114e98adcfef46eebedd64
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07618990B2

Reaction notes

Loading…