Methylamine → N2-(2-(benzo[d]isothiazol-3-ylamino)ethyl)-N5-methylpyridine-2,5-dicarboxamide

HRID 502552Notes

Reaction equation

HRID 502552 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3]([NH:10][CH2:11][CH2:12][NH:13][C:14]([C:16]2[CH:24]=[CH:23][C:19]([C:20]([OH:22])=O)=[CH:18][N:17]=2)=[O:15])=[N:2]1.[C:25](P(=O)(OCC)OCC)#[N:26].CN.C(N(CC)CC)C>ClCCl>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3]([NH:10][CH2:11][CH2:12][NH:13][C:14]([C:16]2[CH:24]=[CH:23][C:19]([C:20]([NH:26][CH3:25])=[O:22])=[CH:18][N:17]=2)=[O:15])=[N:2]1

Participants

6

Reactant 4

HCID 6329MethylamineHCID 8471TriethylamineHCID 76257Diethyl cyanophosphonateHCID 118563616-(2-(Benzo[d]isothiazol-3-ylamino)ethylcarbamoyl)nicotinic acid

Product 1

HCID 11854748N2-(2-(benzo[d]isothiazol-3-ylamino)ethyl)-N5-methylpyridine-2,5-dicarboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 6-(2-(benzo[d]isothiazol-3-ylamino)ethylcarbamoyl)nicotinic acid (62 mg, 0.13 mmol), diethyl cyanophosphonate (21 μL, 0.14 mmol), methylamine (2.0M soln in THF, 15 μL, 0.14 mmol) and triethylamine (20 μL, 0.14 mmol) in dichloromethane (5 mL) was allowed to stir at room temperature overnight. The solution was washed with water, then dried over anhydrous sodium sulfate, filtered and the filtrate concentrated under reduced pressure. Purification by column chromatography, on silica gel, eluting with a mixture of 30% ethyl acetate in hexanes, and selected fractions were combined and concentrated under reduced pressure to yield N2-(2-(benzo[d]isothiazol-3-ylamino)ethyl)-N5-methylpyridine-2,5-dicarboxamide as a white solid, (50 mg). 1H NMR (300 MHz, DMSO-d6): 9.16 (broad s, 1H), 8.99 (s, 1H), 8.79 (m, 1H), 8.37 (d, 1H), 8.23 (t, 2H), 7.91 (d, 1H), 7.58 (s, 1H), 7.49 (t, 1H), 7.39 (t, 1H), 3.61 (m, 3H), 3.34 ppm (m, 4H). MW=355 confirmed by LC-MS, tr=2.98 min (Method B) MH+=356.

Workup

  1. washThe solution was washed with water
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationthe filtrate concentrated under reduced pressure
  5. customPurification by column chromatography
  6. washon silica gel, eluting with a mixture of 30% ethyl acetate in hexanes
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a9b115221f64481baf29217314fb1032
Source dataset
uspto-grants-2010_08
Patent number
US07776847B2

Reaction notes

Loading…