1-Bromo-2-Chloroethane → 3-(3-(1-(2-(2-Chloroethoxy)phenyl)cyclobutylamino)-2-oxopyrazin-1(2H)-yl)-N-cyclopropyl-4-methylbenzamide

HRID 1697367Notes

Reaction equation

[CH:1]1([NH:4][C:5](=[O:32])[C:6]2[CH:11]=[CH:10][C:9]([CH3:12])=[C:8]([N:13]3[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]4([C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=5[OH:30])[CH2:23][CH2:22][CH2:21]4)[C:14]3=[O:31])[CH:7]=2)[CH2:3][CH2:2]1.Br[CH2:34][CH2:35][Cl:36].C(=O)([O-])[O-].[Cs+].[Cs+].C(OCC)(=O)C>C(#N)C.O>[Cl:36][CH2:35][CH2:34][O:30][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=1[C:20]1([NH:19][C:15]2[C:14](=[O:31])[N:13]([C:8]3[CH:7]=[C:6]([CH:11]=[CH:10][C:9]=3[CH3:12])[C:5]([NH:4][CH:1]3[CH2:2][CH2:3]3)=[O:32])[CH:18]=[CH:17][N:16]=2)[CH2:23][CH2:22][CH2:21]1

Participants

Conditions

Temperature: 90 °C

Procedure

To N-cyclopropyl-3-(3-(1-(2-hydroxyphenyl)cyclobutylamino)-2-oxopyrazin-1(2H)-yl)-4-methylbenzamide (Example 268f, 0.874 g) in acetonitrile (17 mL) was added 1-bromo-2-chloroethane (1.68 mL) and cesium carbonate (6.61 g) and the reaction heated at 90° C. for 18 h. Ethyl acetate and water were added and the organic layer separated, washed with water, brine, dried (MgSO4), filtered and the solvent removed in vacuo. Purification (SiO2 chromatography eluting with 50-70% ethyl acetate/iso-hexane) gave the subtitle product (304 mg). The drying agent was re-washed with dichloromethane (2×50 mL) and the solvent removed to afford further subtitle product (472 mg).

Workup

customthe organic layer separated
washwashed with water, brine
dry with materialdried (MgSO4)
filtrationfiltered
customthe solvent removed in vacuo
customPurification (SiO2 chromatography eluting with 50-70% ethyl acetate/iso-hexane)

Sources & evidence

ORD record: ord-d12b8cd4613f48e881efa40d61d01e74
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08163905B2

Reaction notes

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