N-methyl-2-pyrrolidone → HCID 58277336, compound

HRID 1949219Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([N:8]2[C:12]([C:13]3[CH:18]=[CH:17][C:16]([F:19])=[C:15]([Cl:20])[CH:14]=3)=[CH:11][C:10]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[N:9]2)[CH:5]=[CH:6][CH:7]=1.[CH3:26][N:27]1CCCC1=O>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:20][C:15]1[CH:14]=[C:13]([C:12]2[N:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([C:26]#[N:27])[CH:3]=3)[N:9]=[C:10]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH:11]=2)[CH:18]=[CH:17][C:16]=1[F:19]

Participants

Conditions

Temperature: 200 °C

Procedure

100 mg (0.236 mmol) of the compound of Example 51A are provided in 1 ml of 1-methyl-2-pyrrolidone, 55.4 mg (0.472 mmol) of zinc cyanide and 27.3 mg (0.024 mmol) of tetrakis(triphenylphosphine)palladium(0) are added, and the mixture is heated in a closed glass vessel at 200° C. under microwave irradiation for 30 min. The reaction mixture is subsequently filtered through kieselguhr and eluted with methanol, the filtrate is rendered weakly acidic with a 1N aqueous hydrogen chloride solution and concentrated, and the residue is purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient). 33 mg (34% of theory) of the title compound are obtained.

Workup

filtrationThe reaction mixture is subsequently filtered through kieselguhr
washeluted with methanol
concentrationconcentrated
customthe residue is purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient)

Sources & evidence

ORD record: ord-9020e46667cb40e3ae9ea6c5d03221c4
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08399682B2

Reaction notes

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