Sodium Carbonate → N-[5-(2,4-difluorophenyl)-3-(2-methoxyethyl)-1,3-thiazol-2(3H)-ylidene]acetamide

HRID 1470003

Reaction equation

Cl[C:2]1[S:6][C:5](=[N:7][C:8](=[O:10])[CH3:9])[N:4]([CH2:11][CH2:12][O:13][CH3:14])[CH:3]=1.[F:15][C:16]1[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.O.C(O)C.C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:15][C:16]1[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=1[C:2]1[S:6][C:5](=[N:7][C:8](=[O:10])[CH3:9])[N:4]([CH2:11][CH2:12][O:13][CH3:14])[CH:3]=1

Participants

Conditions

Temperature: 85 °C

Procedure

A flask was charged with the product from Example 120A (10.2 g, 42.6 mmol), 2,4-difluorophenylboronic acid (8.08 g, 51.1 mmol), Na2CO3 (64.0 mL of a 2 M aqueous solution, 128 mmol) and PdCl2(PPh3)2 (1.5 g, 2.13 mmol) in 100 mL of DME/H2O/ethanol (7:3:2). The mixture was warmed to 85° C. and stirred overnight. After cooling to room temperature, the mixture was diluted with ethyl acetate and washed with water. The organic extract was dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography on SiO2 using a gradient of 0% to 100% ethyl acetate:hexane to provide 11.5 g (86%) of the title compound: 1H NMR (300 MHz, CDCl3) δ 2.17 (s, 3H) 3.27 (s, 3H) 3.71 (t, J=5.3 Hz, 2H) 4.37 (t, J=5.4 Hz, 2H) 7.17-7.24 (m, 1H) 7.38-7.48 (m, 1H) 7.64-7.74 (m, 1H) 7.88 (s, 1H); MS (ESI+) m/z 313 (M+H)+.

Workup

temperatureAfter cooling to room temperature
washwashed with water
extractionThe organic extract
dry with materialwas dried (MgSO4)
filtrationfiltered
concentrationconcentrated
customThe residue was purified by flash chromatography on SiO2 using a gradient of 0% to 100% ethyl acetate

Sources & evidence

ORD record: ord-8680cef2685d4792b7d4216b68c92552
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09006275B2

Linked notes

Loading…