Methyl iodide → HCID 73776851, compound

HRID 520735Notes

Reaction equation

[C:1]([NH:5][C:6]([C:8]1[CH:13]=[CH:12][C:11]([C:14]#[C:15][C:16]2[CH:21]=[CH:20][N:19]=[C:18]([Cl:22])[CH:17]=2)=[CH:10][N:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].IC.[H-].[Na+].[C:27]([O-])(O)=O.[Na+]>CN(C=O)C>[C:1]([N:5]([CH3:27])[C:6]([C:8]1[CH:13]=[CH:12][C:11]([C:14]#[C:15][C:16]2[CH:21]=[CH:20][N:19]=[C:18]([Cl:22])[CH:17]=2)=[CH:10][N:9]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 2.5 °C

Procedure

(180 mg, 574 μmol) 5-(2-Chloro-pyridin-4-ylethynyl)-pyridine-2-carboxylic acid tert-butylamide (Example 1, step 2) was dissolved in DMF (3 ml) and cooled to 0-5° C. Iodomethane (54 μl, 860 μmol, 1.5 equiv.) and NaH (55%) (41 mg, 860 μmol, 1.5 equiv.) were added and the mixture was stirred for 2 hours without cooling bath. The reaction mixture was treated with sat. NaHCO3 solution and extracted twice with EtOAc. The organic layers were extracted with water, dried over sodium sulfate and evaporated to dryness. The crude product was purified by flash chromatography on silica gel (20 g, ethyl acetate/heptane gradient, 0:100 to 100:0). The desired 5-(2-chloro-pyridin-4-ylethynyl)-pyridine-2-carboxylic acid tert-butyl-methyl-amide (78 mg, 42% yield) was obtained as a yellow solid, MS: m/e=328.4/330.4 (M+H+).

Workup

temperaturewithout cooling bath
extractionextracted twice with EtOAc
extractionThe organic layers were extracted with water
dry with materialdried over sodium sulfate
customevaporated to dryness
customThe crude product was purified by flash chromatography on silica gel (20 g, ethyl acetate/heptane gradient, 0:100 to 100:0)

Sources & evidence

ORD record: ord-da7e4c9afd084c4ab4680e8f633f17b9
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09328070B2

Reaction notes

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