4-tert-Butylcyclohexylamine → HCID 178445674, compound

HRID 2119314Notes

Reaction equation

Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH2:12][C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)=[N:4][N:3]=1.[C:19]([CH:23]1[CH2:28][CH2:27][CH:26]([NH2:29])[CH2:25][CH2:24]1)([CH3:22])([CH3:21])[CH3:20].C(=O)([O-])O.[Na+]>C(OCC)(=O)C>[C:19]([C@@H:23]1[CH2:24][CH2:25][C@H:26]([NH:29][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]([CH2:12][C:13]3[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=3)=[N:4][N:3]=2)[CH2:27][CH2:28]1)([CH3:22])([CH3:20])[CH3:21]

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 1.0 g (3.91 mmol) 1-chloro-4-(4-pyridylmethyl)phthalazine (Example 67.A1 in WO 98/35958) and 1.82 g (11.7 mmol) 4-tert-butylcyclohexylamine (trans-/cis-mixture) is stirred overnight at 120° C. The cooled reaction mixture is then distributed between ethyl acetate and saturated aqueous sodium hydrogencarbonate solution. The organic phase is washed with water and brine, dried (MgSO4) and evaporated and the residue purified on silica gel by flash chromatography using dichloromethane/methanol (9:1) yielding the title compound as a trans-/cis-mixture: FAB MS (M+H)+=375. Separation of the isomers by reversed phase medium pressure chromatography (CH3CN/H2O/trace of TFA) gives the cis-isomer (m.p. 64-65° C.) followed by the trans-isomer (m.p. 132-134° C.).

Workup

customThe cooled reaction mixture
washThe organic phase is washed with water and brine
dry with materialdried (MgSO4)
customevaporated
customthe residue purified on silica gel by flash chromatography

Sources & evidence

ORD record: ord-d49a51c64a2f4621b6ea3d6d4d214eee
Source dataset: uspto-grants-2004_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06686347B2

Reaction notes

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