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

HRID 337107Notes

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-f34fc93b42aa4bda97a8de317e543379
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889692B2

Reaction notes

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