Methyl iodide → 4-(Methyl(pyridin-3-yl)amino)picolinonitrile

HRID 1908978Notes

Reaction equation

[H-].[Na+].[N:3]1[CH:8]=[CH:7][CH:6]=[C:5]([NH:9][C:10]2[CH:15]=[CH:14][N:13]=[C:12]([C:16]#[N:17])[CH:11]=2)[CH:4]=1.[CH3:18]I>C1COCC1.CCOC(C)=O>[CH3:18][N:9]([C:5]1[CH:4]=[N:3][CH:8]=[CH:7][CH:6]=1)[C:10]1[CH:15]=[CH:14][N:13]=[C:12]([C:16]#[N:17])[CH:11]=1

Participants

Conditions

Temperature: 0 °C

Procedure

NaH (185 mg, 7.71 mmol, 1.10 eq) was added to a flame-dried round-bottom flask and anhydrous THF (17.5 mL) was added. The slurry was cooled to 0° C. and compound 10 (1.374 g, 7.003 mmol, 1.000 eq) was added as a solution in THF (17.5 mL). After stirring at 0° C. for 30 minutes methyl iodide (481 μL, 7.71 mmol, 1.10 eq) was added and the reaction was allowed to warm to room temperature while stirring overnight. The reaction was diluted with EtOAc and washed with water (1×). The aqueous layer was back extracted (1×) with EtOAc and the combined organics were washed with brine, dried (MgSO4), filtered and concentrated in vacuo. Purification by flash chromatography on silica gel afforded 473 mg (32%) of the title compound as a white solid: 1H NMR (400 MHz, CDCl3) δ1H NMR (400 MHz, DMSO-d6) δ 8.58 (d, J=2.5 Hz, 1H), 8.56 (dd, J=1.2, 4.7 Hz, 1H), 8.24 (d, J=6.0 Hz, 1H), 7.81 (dq, J=1.4, 8.2 Hz, 1H), 7.56-7.53 (m, 1H), 7.25 (d, J=2.6 Hz, 1H), 6.80 (dd, J=2.7, 6.0 Hz, 1H), 3.36 (s, 3H); ES-MS [M+1]+:211.1.

Workup

additionwas added
temperatureto warm to room temperature
washwashed with water (1×)
extractionThe aqueous layer was back extracted (1×) with EtOAc
washthe combined organics were washed with brine
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated in vacuo
customPurification by flash chromatography on silica gel

Sources & evidence

ORD record: ord-d6585d852eaf4110a14c4639a1ecbdb0
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08598345B2

Reaction notes

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