Chloroacetyl chloride → 2-Chloro-N-[4-(1-ethyl-propylamino)-6-methyl-2-(2,4,6-trimethyl-phenoxy)-pyridin-3-yl]-acetamide

Reaction equation

C(C([C:6]1[C:7]([NH2:24])=[C:8]([NH2:23])[C:9]([O:13][C:14]2[C:19]([CH3:20])=[CH:18][C:17]([CH3:21])=[CH:16][C:15]=2[CH3:22])=[N:10][C:11]=1[CH3:12])CC)C.[Cl:25][CH2:26][C:27](Cl)=[O:28].C(N([CH2:35][CH3:36])CC)C.[CH2:37]1[CH2:41]OC[CH2:38]1>>[Cl:25][CH2:26][C:27]([NH:23][C:8]1[C:9]([O:13][C:14]2[C:15]([CH3:22])=[CH:16][C:17]([CH3:21])=[CH:18][C:19]=2[CH3:20])=[N:10][C:11]([CH3:12])=[CH:6][C:7]=1[NH:24][CH:38]([CH2:35][CH3:36])[CH2:37][CH3:41])=[O:28]

Participants

Reactant 4

HCID 6577Chloroacetyl chloride

HCID 8028Tetrahydrofuran

HCID 8471Triethylamine

HCID 867595891-Ethyl-propyl-6-methyl-2-(2,4,6-trimethyl-phenoxy)-pyridine-3,4-diamine

Product 1

HCID 120183492-Chloro-N-[4-(1-ethyl-propylamino)-6-methyl-2-(2,4,6-trimethyl-phenoxy)-pyridin-3-yl]-acetamide

Procedure

To a solution of N+(1-ethyl-propyl-6-methyl-2-(2,4,6-trimethyl-phenoxy)-pyridine-3,4-diamine (250 mg, 0.763 mmol) in dry THF was added chloroacetyl chloride (86 mg, 0.763 mmol) and triethylamine (77 mg, 0.763 mmol) at 0° C. The resulting mixture was warmed to room temperature and stirred for 1 hr. The mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to dryness to give the title compound as a solid. The solid was purified through silica gel column chromatography to give 280 mg(91%) of tan crystals, mp. 152-154° C.