Ethyl Acetate → [3-(2,2-Difluoro-2-phenyl-ethylamino)-6-methyl-2-oxo-2H-pyrazin-1-yl]-acetic acid ethyl ester

HRID 849017Notes

Reaction equation

Br[C:2]1[C:3](=[O:15])[N:4]([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:5]([CH3:8])=[CH:6][N:7]=1.[F:16][C:17]([F:26])([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH2:18][NH2:19].C(OCC)(=O)C>C1(C)C=CC=CC=1>[F:16][C:17]([F:26])([C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)[CH2:18][NH:19][C:2]1[C:3](=[O:15])[N:4]([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:5]([CH3:8])=[CH:6][N:7]=1

Participants

Conditions

Temperature: 110 °C

Procedure

To a stirred suspension of 507 mg (1.843mmol) of 7-4 in 10 ml of toluene was added 578 mg (3.68 mmol) of 7-6 via pipet. The reaction mixture was heated to 110° C. overnight. The solution was allowed to cool to room temperature and ethyl acetate was added. The diluted reaction mixture was washed with 10% hydrochloric acid. Three ethyl acetate extractions were performed on the aqueous layer. The organic layers were combined, dried (sodium sulfate), and concentrated in vacuo to give 745 mg of an off white solid. The solid was purified using a 40 mm column, 6 inches of silica gel and a 1:1 ethyl acetate/hexane solvent system to give 7-7 as a colorless solid: H1NMR CDCl3): δ 1.25 (t, 3H, 6.2 Hz), 2.1 (s, 3H), 4.0-4.1 (m, 2H), 4.25 (q, 2H, 7.1 Hz), 4.72 (s, 2H), 6.15 (s 1H), 6.68 (s, 1H) 7.4-7.6 (m, 3H), 7.6-7.8 (m, 2H).

Workup

temperatureto cool to room temperature
customThe diluted reaction mixture
washwas washed with 10% hydrochloric acid
extractionThree ethyl acetate extractions
dry with materialdried (sodium sulfate)
concentrationconcentrated in vacuo
customto give 745 mg of an off white solid
customThe solid was purified

Sources & evidence

ORD record: ord-082e302ab0a44bb3993bd9ec935dbb73
Source dataset: uspto-grants-2000_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06011038

Reaction notes

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