3,6-Dichloropyridazine → 4-(Boc-amino)-1-(6-chloro-3-pyridazinyl)piperidine

HRID 2421970Notes

Reaction equation

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

Participants

Conditions

Temperature: 150 °C

Procedure

tert-Butyl piperidin-4-ylcarbamate (2 g, 10 mmol), 3,6-dichloropyridazine (1.79 g, 12 mmol) and TEA (2.1 ml, 15 mmol) was dissolved in dry DMF (30 ml) and the reaction mixture was heated in a microwave reactor at 150° C. for 20 mins. The reaction mixture was diluted with water (300 ml) and extracted with EtOAc (300 ml). The organic phase was dried (Na2SO4), filtrated and evaporated. The residue was purified by silica gel column chromatography using a 98:2 mixture of DCM:MeOH to give the title compound (2.11 g, 68%) as a solid. 1H-NMR (CDCl3, 500 MHz): δ 7.19 (d, 1H), 6.91 (d, 1H), 4.48 (bs, 1H), 4.29-4.20 (m, 2H), 3.73 (bs, 1H), 3.14-3.04 (m, 2H), 2.10-2.02 (m, 2H), 1.49-1.38 (m, 2H), 1.45 (s, 9H); 13C-NMR (CDCl3, 125 MHz): δ 158.9, 155.2, 146.7, 128.9, 115.5, 79.6, 47.9, 44.4, 31.9, 28.5.

Workup

extractionextracted with EtOAc (300 ml)
dry with materialThe organic phase was dried (Na2SO4)
filtrationfiltrated
customevaporated
customThe residue was purified by silica gel column chromatography
additiona 98:2 mixture of DCM

Sources & evidence

ORD record: ord-dd6711dd1daf4cc49aa6ed76dbd8a32c
Source dataset: uspto-grants-2011_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07960380B2

Reaction notes

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