3-Chloro-6-(trifluoromethyl)pyridazine → 1-Cyclobutyl-4-({4-[6-(trifluoromethyl)-3-pyridazinyl]phenyl}carbonyl)hexahydro-1H-1,4-diazepine hydrochloride

HRID 452883Notes

Reaction equation

HRID 452883 reaction equation
[CH:1]1([N:5]2[CH2:11][CH2:10][CH2:9][N:8]([C:12]([C:14]3[CH:19]=[CH:18][C:17](B4OC(C)(C)C(C)(C)O4)=[CH:16][CH:15]=3)=[O:13])[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.[Cl:29][C:30]1[N:31]=[N:32][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:34][CH:35]=1>>[ClH:29].[CH:1]1([N:5]2[CH2:11][CH2:10][CH2:9][N:8]([C:12]([C:14]3[CH:15]=[CH:16][C:17]([C:30]4[N:31]=[N:32][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:34][CH:35]=4)=[CH:18][CH:19]=3)=[O:13])[CH2:7][CH2:6]2)[CH2:2][CH2:3][CH2:4]1

Participants

3

Reactant 2

HCID 282425263-Chloro-6-(trifluoromethyl)pyridazineHCID 66930417(4-Cyclobutylhexahydro-1H-1,4-diazepin-1-yl)[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methanone

Product 1

HCID 669304151-Cyclobutyl-4-({4-[6-(trifluoromethyl)-3-pyridazinyl]phenyl}carbonyl)hexahydro-1H-1,4-diazepine hydrochloride

Procedure

The title compound (E22) was prepared in a similar manner to Example 11 from 1-cyclobutyl-4-{[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbonyl}hexahydro-1H-1,4-diazepine (D7) and 3-chloro-6-(trifluoromethyl)pyridazine (Goodman, Stanforth and Tarbit, Tetrahedron, 1999, 55, 15067). The crude product after work-up was by purified by flash chromatography [silica gel, gradient 0-100% EtOAc-MeOH) and the free base was converted into the title hydrochloride salt (E22). 1H NMR δ (methanol-d4): 1.8-1.95 (2H, m), 2.15-2.48 (6H, m), 3.07-3.25 (2H, m), 3.48-3.95 (6H, m), 4.3-4.5 (1H, m), 7.72 (2H, d, J=8 Hz), 8.21 (1H, d, J=8 Hz), 8.32 (2H, d, J=8 Hz), 8.45 (1H, d, J=8 Hz).

Workup

  1. customby purified by flash chromatography [silica gel, gradient 0-100% EtOAc-MeOH) and the free base

Sources & evidence

ORD record
ord-a9abc71cbb2346b087bcb251ea1d74fd
Source dataset
uspto-grants-2013_07
Patent number
US08492375B2

Reaction notes

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