Ethanolamine → 2-[2-(acetylamino)pyridin-4-yl]-4-(2-chlorophenyl)-N-(2-hydroxyethyl)-1,3-thiazole-5-carboxamide

HRID 1530148Notes

Reaction equation

HRID 1530148 reaction equation
[C:1]([NH:4][C:5]1[CH:10]=[C:9]([C:11]2[S:12][C:13]([C:23](O)=[O:24])=[C:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[Cl:22])[N:15]=2)[CH:8]=[CH:7][N:6]=1)(=[O:3])[CH3:2].C(Cl)Cl.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[CH2:51]([CH2:53][NH2:54])[OH:52]>>[C:1]([NH:4][C:5]1[CH:10]=[C:9]([C:11]2[S:12][C:13]([C:23]([NH:54][CH2:53][CH2:51][OH:52])=[O:24])=[C:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[Cl:22])[N:15]=2)[CH:8]=[CH:7][N:6]=1)(=[O:3])[CH3:2]

Participants

6

Reactant 5

HCID 700EthanolamineHCID 6344DichloromethaneHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 580949642-[2-(Acetylamino)pyridin-4-yl]-4-(2-chlorophenyl)-1,3-thiazole-5-carboxylic acid

Product 1

HCID 668555632-[2-(acetylamino)pyridin-4-yl]-4-(2-chlorophenyl)-N-(2-hydroxyethyl)-1,3-thiazole-5-carboxamideYield 55.4%

Procedure

To a stirred solution of 2-[2-(acetylamino)pyridin-4-yl]-4-(2-chlorophenyl)-1,3-thiazole-5-carboxylic acid (0.050 g, 0.130 mmol) in methylene chloride (3.00 mL, 46.80 mmol) was added N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.056 g, 0.294 mmol) followed by 1-hydroxybenzotriazole (0.040 g, 0.294 mmol) and the resulting solution was stirred for 1 h. Ethanolamine (0.081 mL, 1.340 mmol) was added and the reaction mixture was continued to stir for 18 h. The mixture was quenched by the addition of water (5.0 mL) and extracted with EtOAc (10.0 mL×3). The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography (SiO2, elution with 0-75% EtOAc in hexanes) to provide 0.0300 g of product as a clear colorless oil (54% 2 steps). LC/MS (AA) ES+ 417, 419. 1H NMR (400 MHz, d1 CDCl3) δ: 8.06-7.98 (m, 1H), 7.72-7.54 (m, 3H), 7.49-7.44 (m, 2H), 7.02-6.96 (m, 1H), 6.28 (br s, 1H), 4.72 (br t, J=5.6 Hz, 1H), 4.66 (br t, J=5.4 Hz, 1H), 3.37 (q, J=6.0 Hz, 2H), 3.18 (q, J=6.4 Hz, 2H), 2.12 (s, 3H).

Workup

  1. stirringto stir for 18 h
  2. customThe mixture was quenched by the addition of water (5.0 mL)
  3. extractionextracted with EtOAc (10.0 mL×3)
  4. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography (SiO2, elution with 0-75% EtOAc in hexanes)

Sources & evidence

ORD record
ord-6fbbf9652c51459387f0ecf45561b94b
Source dataset
uspto-grants-2015_07
Patent number
US09090601B2

Reaction notes

Loading…