Triethylamine → N-(2-(benzo[d]isothiazol-3-ylamino)ethyl)-4-chloropicolinamide

HRID 502559Notes

Reaction equation

HRID 502559 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][NH2:13])=[N:2]1.[Cl:14][C:15]1[CH:20]=[CH:19][N:18]=[C:17]([C:21](O)=[O:22])[CH:16]=1.Cl.CN(C)CCCN=C=NCC.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:21](=[O:22])[C:17]2[CH:16]=[C:15]([Cl:14])[CH:20]=[CH:19][N:18]=2)=[N:2]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2308904-Chloropyridine-2-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 16768374N1-(benzo[d]isothiazol-3-yl)ethane-1,2-diamine

Product 1

HCID 11854745N-(2-(benzo[d]isothiazol-3-ylamino)ethyl)-4-chloropicolinamideYield 28.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of N1-(benzo[d]isothiazol-3-yl)ethane-1,2-diamine (100 mg, 0.52 mmol), 4-chloropicolinic acid (90 mg, 0.57 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (98 mg, 0.57 mmol) and triethylamine (174 μL, 1.1 mmol) in dichloromethane (5 mL) was allowed to stir at room temperature overnight. The reaction mixture was washed successively with 1N aqueous hydrochloric acid, saturated sodium bicarbonate solution and water, then dried over anhydrous sodium sulfate, filtered and the filtrate concentrated under reduced pressure. Purification by flash column chromatography, on silica gel, eluting with a mixture of 1% methanol in dichloromethane and selected fractions were combined and concentrated under reduced pressure to give N-(2-(benzo[d]isothiazol-3-ylamino)ethyl)-4-chloropicolinamide (50 mg) as a white solid. 1H NMR (300 MHz, CDCl3): 8.66 (broad s, 1H), 8.41 (d, 1H), 8.20 (s, 1H), 7.78 (t, 2H), 7.65-7.38 (m, 3H), 5.95 (broad s, 1H), 3.84 ppm (m, 4H). MW=333 confirmed by LC-MS, tr=12.38 min (Method Y) MH+=334.

Workup

  1. washThe reaction mixture was washed successively with 1N aqueous hydrochloric acid, saturated sodium bicarbonate solution and water
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationthe filtrate concentrated under reduced pressure
  5. customPurification by flash column chromatography
  6. washon silica gel, eluting with a mixture of 1% methanol in dichloromethane
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-96b0ec4a6dc348089970ba50d26ef600
Source dataset
uspto-grants-2010_08
Patent number
US07776847B2

Reaction notes

Loading…