Acetic Anhydride → HCID 178522951, compound

HRID 2307299Notes

Reaction equation

[Cl:1][C:2]1[CH:27]=[CH:26][C:5]([CH2:6][NH:7][C:8](=[O:25])[CH2:9][C:10]([C:12]2[CH:16]=[C:15]([CH2:17][N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[S:14][C:13]=2[Cl:24])=[O:11])=[CH:4][CH:3]=1.C(OC(OCC)OCC)C.[C:38]([O:41][C:42](=O)[CH3:43])(=O)[CH3:39].[NH2:45][CH2:46][CH2:47][N:48]1CCOC[CH2:49]1>C(O)C>[Cl:1][C:2]1[CH:27]=[CH:26][C:5]([CH2:6][NH:7][C:8](=[O:25])[C:9]([C:10]([C:12]2[CH:16]=[C:15]([CH2:17][N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[S:14][C:13]=2[Cl:24])=[O:11])=[CH:49][NH:48][CH2:47][CH2:46][N:45]2[CH2:43][CH2:42][O:41][CH2:38][CH2:39]2)=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of N-(4-chlorobenzyl)-3-(2-chloro-5-(morpholin-4-ylmethyl)thien-3-yl)-3-oxopropanamide (Preparation 20, 20.0 g), triethylorthoformate (15.4 mL), and acetic anhydride (15.4 mL) is heated to 150° C. with removal of the distillate with a Dean-Stark trap. After 3 h, the volatiles are removed at 40 Torr (50° C.) and then at 0.2 Torr (100° C.) for 1 h to afford a brown oil. A portion of this residue (10.0 g) is dissolved in ethanol (150 mL) and N-aminoethylmorpholine (4.1 g) is added. The mixture is stirred at room temperature for 24 h and then is concentrated in vacuo. The crude product is purified by column chromatography (CH2Cl2/methanol, 97/3) to afford 4.28 g of the title compound as a brown oil. Physical characteristics. 1H NMR (300 MHz, DMSO-d6) δ 10.51, 9.89, 7.62, 7.58, 7.37, 6.92, 4.44, 3.62, 3.58, 3.47, 3.40, 2.42, 2.32.

Workup

customthe volatiles are removed at 40 Torr (50° C.)
customat 0.2 Torr (100° C.) for 1 h to afford a brown oil
concentrationis concentrated in vacuo
customThe crude product is purified by column chromatography (CH2Cl2/methanol, 97/3)

Sources & evidence

ORD record: ord-e362de9e035945579809f37d2133ba32
Source dataset: uspto-grants-2004_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06831081B2

Reaction notes

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