Triethylamine → N-(4-chloro-2-(pyridin-3-yl)thiazol-5-yl)-N-ethyl-2-methyl-3-(methylthio)propanamide

HRID 533327Notes

Reaction equation

HRID 533327 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)[S:5][C:6]=1[NH:7][CH2:8][CH3:9].[CH3:16][CH:17]([CH2:21][S:22][CH3:23])[C:18](O)=[O:19].C(N(CC)CC)C.Cl.CN(C)CCCN=C=NCC>ClC(Cl)C>[Cl:1][C:2]1[N:3]=[C:4]([C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)[S:5][C:6]=1[N:7]([CH2:8][CH3:9])[C:18](=[O:19])[CH:17]([CH3:16])[CH2:21][S:22][CH3:23]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 136944152-Methyl-3-(methylsulfanyl)propanoic acidHCID 59580448(4-Chloro-2-pyridin-3-yl-thiazol-5-yl)-ethylamine

Product 1

HCID 49805426N-(4-chloro-2-(pyridin-3-yl)thiazol-5-yl)-N-ethyl-2-methyl-3-(methylthio)propanamideYield 60.3%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of (4-chloro-2-pyridin-3-yl-thiazol-5-yl)-ethylamine (800 mg, 3.33 mmol) in dichloroethane (30 mL) was added 2-methyl-3-methylsulfanyl-propionic acid (prepared according to literature reference J. Org. Chem. 1996, 51, 1026-1029) (894 mg, 6.66 mmol) and N,N-dimethylaminopyridine (814 mg, 6.66 mmol) followed by triethylamine (0.2 mL, 1.44 mmol). To this was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.92 g, 9.99 mmol). The reaction mixture was stirred at ambient temperature for 16 h. The reaction mixture was concentrated and the crude product was purified by silica gel chromatography (0 to 100% ethyl acetate/hexanes) to afford a beige solid (715 mg, 60%): mp 79-81° C.; 1H NMR (300 MHz, CDCl3) δ 9.11 (d, J=1.7 Hz, 1H), 8.71 (d, J=4.8 Hz, 1H), 8.27-8.13 (m, 1H), 7.42 (dd, J=8.0, 4.9 Hz, 1H), 3.90 (bs, 1H), 3.69 (bs, 1H), 2.80 (bs, 2H), 2.47 (bs, 1H), 2.02 (s, 3H), 1.21 (q, J=7.3 Hz, 6H); ESIMS m/z 356 (M+1).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe crude product was purified by silica gel chromatography (0 to 100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-728ad0fcd7c343908a26221dc118c96c
Source dataset
uspto-grants-2014_10
Patent number
US08853246B2

Reaction notes

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