Ethyl Acetate → HCID 5276326, compound

Temperature

90 °C

N-(4-Chlorobenzyl)-2-(chloromethyl)-7-methyl-4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxamide (Preparation 1, 134 mg) and (S)-(3R)-morpholin-3-yl(phenyl)methanol hydrochloride (Preparation 9, 111 mg) in DMF (3 mL) is treated with diisopropylethylamine (0.5 mL). The mixture is heated at 90° C. overnight. After cooling to room temperature, the solution is poured into ethyl acetate (75 mL) and washed with dilute pH 4 phosphate buffer (10 mL), dilute pH 7 phosphate buffer (10 mL), and brine (10 mL). The organic layer is dried (Na2SO4), filtered and concentrated under reduced pressure. The resulting residue is purified by flash column chromatography (methanol/CH2Cl2, 1-3%) and ethyl acetate-hexanes crystallization to afford 0.13 g of the title compound Physical characteristics. M.p. 129-134° C.; 1H NMR (400 MHz, DMSO-d6) δ 10.60, 8.67, 7.41-7.25, 5.33, 5.07, 4.54, 4.17, 3.88, 3.81, 3.73, 3.6, 3.5-3.4, 2.94, 2.6, 2.4-2.3; HRMS m/z 538.1561 (M+H)+. Anal. Found: C, 62.33; H, 5.25; N, 7.75.

1. temperatureAfter cooling to room temperature
2. washwashed
3. additionwith dilute pH 4 phosphate buffer (10 mL)
4. additiondilute pH 7 phosphate buffer (10 mL), and brine (10 mL)
5. dry with materialThe organic layer is dried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe resulting residue is purified by flash column chromatography (methanol/CH2Cl2, 1-3%) and ethyl acetate-hexanes crystallization

ORD record

ord-754b4870eed943dda859d225e578dada

Source dataset

uspto-grants-2004_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06831081B2