HCID 16772160, compound → HCID 11719943, compound

HRID 1921455Notes

Reaction equation

HRID 1921455 reaction equation
[CH:1]1([NH:4][CH:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=2)[CH3:6])[CH2:3][CH2:2]1.[CH2:13]([C:15]1[C:20](=[O:21])[NH:19][C:18]([CH3:22])=[C:17]([C:23]2[S:27][C:26]([S:28](Cl)(=[O:30])=[O:29])=[CH:25][CH:24]=2)[CH:16]=1)[CH3:14]>ClCCl>[CH:1]1([N:4]([CH:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=2)[CH3:6])[S:28]([C:26]2[S:27][C:23]([C:17]3[CH:16]=[C:15]([CH2:13][CH3:14])[C:20](=[O:21])[NH:19][C:18]=3[CH3:22])=[CH:24][CH:25]=2)(=[O:29])=[O:30])[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 16772160HCID 16772160, compoundHCID 866103525-(5-Ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonyl chloride

Product 1

HCID 11719943HCID 11719943, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of cyclopropyl(1-pyridin-2-yl)ethylamine (73.5 mg, 0.453 mmol), 5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonyl chloride (144 mg, 0.453 mmol), PS-piperidinomethyl (155 mg, 0.542 mmol, beads) and dichloromethane (5 mL) is stirred at room temperature overnight. The reaction mixture is filtered and the filtrate is evaporated. The residue is purified by chromatography on an ISCO Redisep 10 g cartridge eluting with ethyl acetate-5% methanol to afford 5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonic acid cyclopropyl(1-pyridin-2-yl)ethylamide (85 mg, 43% yield) as a white solid. A hydrochloride salt is prepared by dissolving the amine (85 mg, 0.192 mmol) in methanol (2 mL), adding 1 M ethereal hydrochloric acid (0.3 mL), some methanol is removed, more ether added and the hydrochloride salt is collected by filtration (50 mg, 54% yield as an off white solid). RT=2.93 min; m/e=444; 1H NMR (δ, ppm): 11.84 (1H, br s), 8.6 (1H, d), 8.02 (1H, m), 7.69 (1H, d), 7.61 (1H, d), 7.50 (1H, m), 7.37 (1H, s), 5.24 (1H, d), 5.27 (2H, m), 2.40 (2H, m), 2.33 (3H, s), 1.53 (3H, d), 1.13 (3H, t), 0.6-0.96 (4H, m).

Workup

  1. filtrationThe reaction mixture is filtered
  2. customthe filtrate is evaporated
  3. customThe residue is purified by chromatography on an ISCO Redisep 10 g cartridge
  4. washeluting with ethyl acetate-5% methanol

Sources & evidence

ORD record
ord-d766cab1c5dd421d88bc76581b034f2c
Source dataset
uspto-grants-2012_05
Patent number
US08173682B2

Reaction notes

Loading…