4-tert-Butylcyclohexylamine → HCID 178445675, compound

HRID 1072544Notes

Reaction equation

HRID 1072544 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH2:12][CH2:13][C:14]2[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=2)=[N:4][N:3]=1.[C:20]([CH:24]1[CH2:29][CH2:28][CH:27]([NH2:30])[CH2:26][CH2:25]1)([CH3:23])([CH3:22])[CH3:21]>C(OCC)(=O)C.O.N>[C:20]([C@@H:24]1[CH2:25][CH2:26][C@H:27]([NH:30][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]([CH2:12][CH2:13][C:14]3[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=3)=[N:4][N:3]=2)[CH2:28][CH2:29]1)([CH3:23])([CH3:21])[CH3:22]

Participants

6

Reactant 2

HCID 793964-tert-ButylcyclohexylamineHCID 22386465HCID 22386465, compound

Product 1

HCID 178445675HCID 178445675, compound

Reagents, catalysts & solvents 3

HCID 222AmmoniaSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

Under N2-atmosphere, 500 mg (1.85 mmol) 1-chloro-4-[2-(pyridin-3-yl)ethyl]phthalazine and 1.25 g (8 mmol) of 4-tert.-butylcyclohexylamine (trans/cis mixture) are heated at 150° C. for 2.5 h. The reaction mixture is diluted with ethyl acetate, water and conc. NH3-solution (=1 ml), then the aqueous layer is separated off and extracted 2× with ethyl acetate. The organic phases are washed twice with water and brine, dried (Na2SO4) and concentrated. Chromatography (SiO2; ethyl acetate to ethyl acetate/ethanol 10:1) yields the trans isomer followed by the cis isomer of the title compound. trans 1-(4-tert.-Butylcyclohexylamino)-4-[(2-(pyridin-3-yl)ethyl]phthalazine: m.p. 155-157° C.; 1H-NMR (DMSO-d6) 8.50 (s, 1H), 8.38 (d, 1H), 8.35 (d, 1H), 8.06 (d, 1H), 7.83 (m, 2H), 7.74 (d, 1H), 7.30 (m, 1H), 6.89 (d, HN), 4.08 (m, 1H), 3.38 (t, 2H), 3.10 (t, 2H), 2.12 (m, 2H), 1.81 (m, 2H), 1.35 (q, 2H), 1.14 (q, 2H), 1.07 (m, 1H), 0.88 (s, 9H); FAB-MS (M+H)+=389. cis 1-(4-tert.-Butylcyclohexylamino)-4-[(2-(pyridin-3-yl)ethyl]phthalazine: 1H-NMR (DMSO-d6) 8.48 (m, 2H), 8.38 (d, 1H), 8.08 (m, 1H), 7.84 (m, 2H), 7.73 (m, 1H), 7.29 (m, 1H), 6.49 (d, HN), 4.33 (sb, 1H), 3.39 (m, 2H), 3.10 (m, 2H), 2.18 (d, 2H), 1.6-1.4 (m, 6H), 1.06 (m, 1H), 0.87 (s, 9H); FAB-MS (M+H)+-=389.

Workup

  1. customthe aqueous layer is separated off
  2. extractionextracted 2× with ethyl acetate
  3. washThe organic phases are washed twice with water and brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customChromatography (SiO2; ethyl acetate to ethyl acetate/ethanol 10:1) yields the trans isomer

Sources & evidence

ORD record
ord-e857cbeca8474be89dfbe5a293203bb2
Source dataset
uspto-grants-2005_06
Patent number
US06911440B2

Reaction notes

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