Diisopropylamine → N-(4-Chlorobenzyl)-2-formyl-4-methyl-7-oxo-3-{[2-(trimethylsilyl)ethoxy]methyl}4,7-dihydrothieno[3,2-b]pyridine-6-carboxamide

HRID 23640Notes

Reaction equation

[Cl:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11](=[O:28])[C:12]3[S:19][CH:18]=[C:17]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[C:13]=3[N:14]([CH3:16])[CH:15]=2)=[O:9])=[CH:4][CH:3]=1.[Li+].CC([N-]C(C)C)C.C(NC(C)C)(C)C.C([Li])CCC.C1C[O:54][CH2:53]C1>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11](=[O:28])[C:12]3[S:19][C:18]([CH:53]=[O:54])=[C:17]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:26])([CH3:25])[CH3:27])[C:13]=3[N:14]([CH3:16])[CH:15]=2)=[O:9])=[CH:29][CH:30]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a cold (−78° C.), stirred mixture of 2.03 g of N-(4-chlorobenzyl)-4-methyl-7-oxo-3-{[2-(trimethylsilyl)ethoxy]methyl}-4,7-dihydrothieno[3,2-b]pyridine-6-carboxamide in 50 mL of dry TBF is added via cannula a solution of LDA, prepared as usual in 25 mL of dry THF from 2.5 mL of diisopropylamine and 5.3 mL of a 2.5 M solution of butyllithium in hexanes. The resulting deeply colored solution is stirred for 5 min at −78° C., then 1.7 mL of dry DMF is added, causing the mixture to solidify. The mixture is allowed to warm to 0° C. whereupon it becomes fluid, and is quenched with 50 mL of 1N HCl. Aqueous workup (CH2Cl2, dil. HCl) followed by flash chromatography on silica gel using 30-40% EtOAc in CH2Cl2 affords 1.56 g of the title compound as a yellow solid. Recrystallization from EtOAc provides pale yellow crystals.

Workup

additionis added via cannula
stirringThe resulting deeply colored solution is stirred for 5 min at −78° C.
temperatureto warm to 0° C. whereupon it
customis quenched with 50 mL of 1N HCl

Sources & evidence

ORD record: ord-892d110c6a9741b0bcc66cd0c61ba684
Source dataset: uspto-grants-2005_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06852731B2

Reaction notes

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