4,6-Dichloropyrimidine → HCID 86677061, compound

HRID 1626920Notes

Reaction equation

Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[CH:4][N:3]=1.[NH2:9][C@H:10]([C:12]1[N:13]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:14](=[O:23])[C:15]2[C:20]([CH:21]=1)=[CH:19][CH:18]=[CH:17][C:16]=2[Cl:22])[CH3:11]>O1CCOCC1.C(Cl)Cl.C(O)(=O)C.[Cl-].[Na+].O>[Cl:22][C:16]1[CH:17]=[CH:18][CH:19]=[C:20]2[C:15]=1[C:14](=[O:23])[N:13]([C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)[C:12]([C@@H:10]([NH:9][C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[CH:4][N:3]=1)[CH3:11])=[CH:21]2

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of 4,6-dichloropyrimidine (200 mg, 1.34 mmol, 1.6 eq.), compound 1 (250 mg, 0.84 mmol, 1.0 eq.), and TEA (350 μL, 2.5 mmol, 3.0 eq.) in 1,4-dioxane (7.5 mL) was heated at 60° C. for 3 days. The reaction was charged with additional 4,6-dichloropyrimidine (100 mg, 0.67 mmol, 0.8 eq.) and TEA (175 μL, 1.3 mmol, 1.5 eq.) and heated at 80° C. for 16 h. The reaction mixture was diluted with DCM, 5% aqueous acetic acid, and brine (50 mL each), separated, and the organic phase was washed with 0.1 M NaOH and brine (15 mL each), dried on Na2SO4, and concentrated. The residue was purified by flash chromatography eluting with 300 mL each 10/20/30/40/50% EtOAc/hexanes to give (S)-8-chloro-3-(1-(6-chloropyrimidin-4-ylamino)ethyl)-2-phenylisoquinolin-1(2H)-one 77. ESI-MS m/z: 411.14 [M+H]+.

Workup

temperatureheated at 80° C. for 16 h
customseparated
washthe organic phase was washed with 0.1 M NaOH and brine (15 mL each)
customdried on Na2SO4
concentrationconcentrated
customThe residue was purified by flash chromatography
washeluting with 300 mL each 10/20/30/40/50% EtOAc/hexanes

Sources & evidence

ORD record: ord-7fb2d2835c5949a5b967269744a89eeb
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08785470B2

Reaction notes

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