Acetic Acid → (3-Methylpyridin-2-yl)methanamine acetic acid salt

To a solution of 3-methyl-2-cyanopyridine (5 g) in acetic acid was added 10% Pd/C. The Parr shaker bottle was evacuated/H2 purged 3×, and then shaken at 50 psi until starting material was consumed (typically <1 h). The reaction was filtered through diatomaceous earth and concentrated to yield (3-methylpyridin-2-yl)methanamine acetic acid salt which was used without further purification. To the crude salt in THF was added aq 1 M NaOH, followed by BOC2O (2 eq). The reaction was allowed to stir at rt overnight. After ˜16 h, the reaction mixture was transferred to a separatory funnel, diluted with EtOAc, and water, and the layers were separated. The organic layer was washed with brine, dried (MgSO4), and concentrated in vacuo to give a crude residue which was purified by chromatography on silica gel (EtOAc/hex) to afford tert-butyl ((3-methylpyridin-2-yl)methyl)carbamate. To a solution of the BOC-protected pyridylamine in MeOH was added Nishimura's catalyst. The parr shaker bottle was evacuated/purged with H2 (3×) and then shaken at 50 psi for 24 h. The reaction was filtered through diatomaceous earth, and concentrated in vacuo to give the title compound as a near colorless oil, and was used without further purification. 1H NMR (d6-DMSO, 400 MHz) δ 6.7 (br s, NH), 4.0 (br s, 1H), 2.9-2.7 (m, 3H), 2.6-2.5 (m, 1H), 2.5-2.4 (m, 1H), 1.7-1.6 (br s, 1H), 1.6-1.45 (m, 3H), 1.4 (s, 9H), 1.3-1.2 (m, 1H), 0.8 (d, 3H).

1. customThe Parr shaker bottle was evacuated/H2
2. custompurged 3×
3. customwas consumed (typically <1 h)
4. filtrationThe reaction was filtered through diatomaceous earth
5. concentrationconcentrated

ORDレコード

ord-46b41cb6b2734262bc9708515fc81322

出典データセット

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09440982B2