Triphenylphosphine → 5-(5-Methoxy-pyridin-2-ylmethoxy)-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one

HRID 1425752Notes

Reaction equation

C(O[C:9]1[CH:14]=[N:13][N:12]([CH2:15][C:16]([C:18]2C=CC(CO)=[CH:20][C:19]=2C)=O)[C:11](=[O:27])[CH:10]=1)C1C=CC=CC=1.[CH3:28][O:29][C:30]1[CH:31]=[CH:32][C:33]([CH2:36][OH:37])=[N:34][CH:35]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=[O:60]>C1COCC1>[CH3:28][O:29][C:30]1[CH:31]=[CH:32][C:33]([CH2:36][O:37][C:9]2[CH:14]=[N:13][N:12]([CH:15]3[CH2:16][CH2:18][CH2:19][CH2:20][O:60]3)[C:11](=[O:27])[CH:10]=2)=[N:34][CH:35]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 5-hydroxy-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one (described in preparation 5a of WO 08/022,979, 705 mg, 3.59 mmol) and (5-methoxy-pyridin-2-yl)-methanol (Milestone Pharmtech, 500 mg, 3.59 mmol) in THF (10 mL) is added polymer-bound triphenylphosphine (2.40 g, 3 mmol/g, 7.2 mmol). After cooling to 0° C., diisopropyl azodicarboxylate (1.42 mL, 7.2 mmol) is added slowly. Afterwards, the reaction mixture is stirred for 3 h at room temperature. The reaction mixture is filtered and the solvent is evaporated. The residue is purified via reverse phase HPLC chromatography (Waters XBridge 5 μm, gradient 5%→90% acetonitrile in water+0.3% NH4OH).

Workup

filtrationThe reaction mixture is filtered
customthe solvent is evaporated
customThe residue is purified via reverse phase HPLC chromatography (Waters XBridge 5 μm, gradient 5%→90% acetonitrile in water+0.3% NH4OH)

Sources & evidence

ORD record: ord-01b0ef6065d540ae8634518c83089b9e
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08933079B2

Reaction notes

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