Potassium Phosphate, Tribasic → 4-(1H-indol-4-ylamino)-5-[4-methoxy-3-(2-methoxyethoxy)phenyl]nicotinonitrile

HRID 506158

Reaction equation

Cl[C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[CH:4][C:3]=1[C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH2:19][CH2:20][O:21][CH3:22])[CH:11]=1.[NH2:23][C:24]1[CH:32]=[CH:31][CH:30]=[C:29]2[C:25]=1[CH:26]=[CH:27][NH:28]2.CN(C1C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=CC=CC=1)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>COCCOC.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH:28]1[C:29]2[C:25](=[C:24]([NH:23][C:2]3[C:7]([C:8]#[N:9])=[CH:6][N:5]=[CH:4][C:3]=3[C:10]3[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH2:19][CH2:20][O:21][CH3:22])[CH:11]=3)[CH:32]=[CH:31][CH:30]=2)[CH:26]=[CH:27]1

Participants

Conditions

Temperature: 90 °C

Procedure

To a stirred solution of 4-chloro-5-[4-methoxy-3-(2-methoxyethoxy)phenyl]-nicotinonitrile (100 mg, 0.313 mmol), 4-aminoindole (62 mg, 0.47 mmol), DavePhos (37 mg, 0.094 mmol), and K3PO4 (99.8 mg, 0.47 mmol) in 4 mL of anhydrous ethylene glycol dimethyl ether was added Pd2(dba)3 (28.7 mg, 0.031 mmol). The mixture was heated to 90° C. for 2 h, then cooled, filtered through celite, concentrated in vacuo, and crystallized by tritration with ether/hexane to yield 42.5 mg (33% yield) of the title compound 153 as a tan solid. MS: 415.1 (M+H), HPLC retention time: 7.70 min(b).

Workup

temperaturecooled
filtrationfiltered through celite
concentrationconcentrated in vacuo
customcrystallized by tritration with ether/hexane

Sources & evidence

ORD record: ord-feed64999c964000b05bdf1cd65abd7b
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07781591B2

Linked notes

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