Water → 6-Chloro-2-methyl-4-(5-(1-methylpiperidin-4-yl)pyridin-2-ylamino)pyridazin-3(2H)-one

HRID 337276Notes

Reaction equation

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

Participants

Conditions

Temperature: 70 °C

Procedure

The tert-butyl 4-(6-(6-chloro-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)piperidine-1-carboxylate (2.0 g, 4.76 mmol, Eq: 1.00) was dissolved in the solvent mixture of formic acid (40.0 ml) and formaldehyde, 37% (80.0 ml). The reaction mixture was stirred at 70° C. overnight until reaction was complete as determined by LCMS analysis, then cooled to ambient temperature. Water was added and the resultant aqueous mixture was washed with CH2Cl2 and the CH2Cl2 layer was discarded. The pH of the aqueous layer was adjusted to pH=12 carefully with solid K2CO3, which resulted in precipitation of a solid. The solid was collected by filtration, washed with water and dried in vacuum oven at 50° C. over 72 h to afford 1.4 g of the desired product. (M+H)+=334 m/e. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.84 (dd, J=8.31, 3.02 Hz, 4 H) 1.99-2.19 (m, 2 H) 2.35 (s, 3 H) 2.42-2.68 (m, 1 H) 3.02 (d, J=12.09 Hz, 2 H) 3.81 (s, 3 H) 6.86 (d, J=8.31 Hz, 1 H) 7.52 (dd, J=8.50, 2.46 Hz, 1 H) 8.16-8.33 (m, 3 H).

Workup

temperaturecooled to ambient temperature
washthe resultant aqueous mixture was washed with CH2Cl2
customresulted in precipitation of a solid
filtrationThe solid was collected by filtration
washwashed with water
customdried in vacuum oven at 50° C. over 72 h

Sources & evidence

ORD record: ord-8e4065ef91c14634994c89a7ee86d81a
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889682B2

Reaction notes

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