Potassium Carbonate → Ethyl 6-(2-cyanophenyl)-4-(3-fluorophenethylamino)nicotinate

HRID 2074436Notes

Reaction equation

Cl[C:2]1[CH:12]=[C:11]([NH:13][CH2:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=2)[C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][N:3]=1.[C:23]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1B(O)O)#[N:24].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.Cl[Pd]Cl.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[C:23]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[C:2]1[CH:12]=[C:11]([NH:13][CH2:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=2)[C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][N:3]=1)#[N:24]

Participants

Conditions

Temperature: 100 °C

Procedure

To a mixture of ethyl 6-chloro-4-(3-fluorophenethylamino)nicotinate (1.2 g, 3.7 mmol), 2-cyano-phenylboronic acid (1.1 g, 7.4 mmol) and K2CO3 (1.5 g, 11.1 mmol) in DMF (25 mL) was added PdCl2.dppf (0.2 g, 0.37 mmol). The reaction mixture was stirred at 100° C. for 4 h. LC/MS indicated the reaction was complete. The reaction mixture was filtered and the filtrate was concentrated. The resulting residue was purified on RP-HPLC using a mixture of acetonitrile and H2O to give ethyl 6-(2-cyanophenyl)-4-(3-fluorophenethylamino)nicotinate (500 mg, 34%). LRMS (M+H+) m/z 389.0.

Workup

filtrationThe reaction mixture was filtered
concentrationthe filtrate was concentrated
customThe resulting residue was purified on RP-HPLC
additiona mixture of acetonitrile and H2O

Sources & evidence

ORD record: ord-a0247eb7633f4a1fa8fa27890f312b21
Source dataset: uspto-grants-2011_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07919511B2

Reaction notes

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