Acetic Acid → 6-chloro-4-(5-(1-ethylpiperidin-4-yl)pyridin-2-ylamino)-2-methylpyridazin-3(2H)-one

HRID 1431115Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([CH:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1.[CH:23](=O)[CH3:24].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>O.C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([CH:17]3[CH2:22][CH2:21][N:20]([CH2:23][CH3:24])[CH2:19][CH2:18]3)=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1

Participants

Conditions

Temperature: 0 °C

Procedure

In a 100 mL round-bottomed flask, 6-chloro-2-methyl-4-(5-(piperidin-4-yl)pyridin-2-ylamino)pyridazin-3(2H)-one (179 mg, 560 μmol, Eq: 1.00) and acetaldehyde (247 mg, 316 μl, 5.6 mmol, Eq: 10.0) were combined with THF (5.0 ml) to give a light yellow solution. Acetic acid (33.6 mg, 32.0 μl, 560 μmol, Eq: 1.00) was added. The reaction mixture was cooled to 0° C. Sodium triacetoxyborohydride (178 mg, 840 μmol, Eq: 1.5) was added. The reaction mixture stirred at room temperature for 2 h. The reaction was poured into water, and then saturated NaHCO3 was added to the solution until it was basic. The solution was extracted twice with EtOAc, and then the organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo to give a solid. The solid was triturated with ether to give 6-chloro-4-(5-(1-ethylpiperidin-4-yl)pyridin-2-ylamino)-2-methylpyridazin-3(2H)-one (121 mg, 62%). LC/MS-ESI observed [M+H]+ 348.

Workup

customto give a light yellow solution
extractionThe solution was extracted twice with EtOAc
washthe organic layers were washed with brine
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
customto give a solid
customThe solid was triturated with ether

Sources & evidence

ORD record: ord-36c779a83bde4b7998d2e57813819095
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08940741B2

Reaction notes

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