4-(Tributylstannyl)pyridazine → N-(5-(3-fluorophenyl)pyridin-2-yl)-2-(5-methyl-6-(pyridazin-4-yl)pyridin-3-yl)acetamide

HRID 592148Notes

Reaction equation

Cl[C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=3)=[CH:14][N:13]=2)=[O:10])=[CH:4][C:3]=1[CH3:25].C([Sn](CCCC)(CCCC)[C:31]1[CH:36]=[CH:35][N:34]=[N:33][CH:32]=1)CCC>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.CN(C=O)C>[F:24][C:20]1[CH:19]=[C:18]([C:15]2[CH:16]=[CH:17][C:12]([NH:11][C:9](=[O:10])[CH2:8][C:5]3[CH:6]=[N:7][C:2]([C:31]4[CH:36]=[CH:35][N:34]=[N:33][CH:32]=4)=[C:3]([CH3:25])[CH:4]=3)=[N:13][CH:14]=2)[CH:23]=[CH:22][CH:21]=1

Participants

Conditions

Temperature: 120 °C

Procedure

To a reaction tube containing 2-(6-chloro-5-methylpyridin-3-yl)-N-(5-(3-fluorophenyl)pyridin-2-yl)acetamide 74-5 (54 mg, 0.15 mmol), 4-(tributylstannyl) pyridazine (55 mg, 0.15 mmol) and Pd(PPh3)4 (16 mg, 0.015 mmol) under Argon was added DMF (0.8 mL). The mixture was stirred at 120° C. for 10 hours. The crude product was purified by reverse phase HPLC to give N-(5-(3-fluorophenyl)pyridin-2-yl)-2-(5-methyl-6-(pyridazin-4-yl)pyridin-3-yl)acetamide 74 as white solid. MS m/z 400.1 (M+1); 1H NMR 400 MHz (CDCl3) δ 9.42 (dd, 1H, J1=4.8 Hz, J2=1.2 Hz), 9.29 (dd, 1H, J1=10.4 Hz, J2=1.2 Hz), 8.56 (d, 1H, J=1.6 Hz), 8.46 (d, 1H, J=1.6 Hz), 8.28 (d, 1H, J=8.8 Hz), 7.90 (dd, 1H, J1=17.6 Hz, J2=2.4 Hz), 7.72 (d, 1H, J=1.6 Hz), 7.70 (dd, 1H, J1=10.8 Hz, J2=2.0 Hz), 7.44-7.39 (m, 1H), 7.32-7.30 (m, 1H), 7.25-7.21 (m, 1H), 7.09-7.04 (m, 1H), 3.82 (s, 2H), 2.44 (s, 3H).

Workup

customThe crude product was purified by reverse phase HPLC

Sources & evidence

ORD record: ord-c01d4727130a4d1aa1f75c76e4e7b855
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09238646B2

Reaction notes

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