Potassium Carbonate → 2-(3,4-dichlorophenyl)-5-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridazin-3(2H)-one

HRID 386561Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[C:14](=[O:15])[CH:13]=[C:12]([O:16][CH:17]3[CH2:22][CH2:21][N:20]([C:23]4[N:28]=[CH:27][C:26]([CH2:29][CH2:30][CH3:31])=[CH:25][N:24]=4)[CH2:19][CH2:18]3)[C:11](C(O)=O)=[N:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].C([O-])([O-])=O.[K+].[K+]>CN1C(=O)CCC1>[Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[C:14](=[O:15])[CH:13]=[C:12]([O:16][CH:17]3[CH2:22][CH2:21][N:20]([C:23]4[N:24]=[CH:25][C:26]([CH2:29][CH2:30][CH3:31])=[CH:27][N:28]=4)[CH2:19][CH2:18]3)[CH:11]=[N:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

Conditions

Temperature: 150 °C

Procedure

To a stirring solution of 1-(3,4-dichlorophenyl)-6-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)-1,6-dihydropyridazine-3-carboxylic acid (15 mg, 0.03 mmol) in NMP (2 mL) at room temperature under argon was added K2CO3 (8.22 mg, 0.06 mmol). The reaction mixture was heated at 150° C. overnight. The crude product was directly purified by preparative HPLC (C18 column; 10-100% methanol in water without TFA) to give 2-(3,4-dichlorophenyl)-5-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridazin-3(2H)-one (9.5 mg, tan solid, 66%). 1H NMR (400 MHz, CDCl3) δ ppm 0.93 (t, J=7.47 Hz, 2H) 1.38-1.72 (m, 2H) 1.81-2.02 (m, 2H) 2.00-2.21 (m, 2H) 2.40 (t, J=7.69 Hz, 2H) 3.50-3.80 (m, 2H) 4.06-4.37 (m, 2H) 4.47-4.68 (m, 1H) 5.56 (s, 1H) 7.28 (dd, J=8.57, 2.42 Hz, 2H) 7.44-7.72 (m, 2H) 8.16 (s, 2H). MS (ESI) 461 (M+H).

Workup

customThe crude product was directly purified by preparative HPLC (C18 column; 10-100% methanol in water without TFA)

Sources & evidence

ORD record: ord-02b974a1d97042d99487cef62654e6a5
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08372837B2

Reaction notes

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