1,2-Diaminocyclohexane, trans- → HCID 86722438, compound

HRID 718832Notes

Reaction equation

HRID 718832 reaction equation
[CH2:1]([C:3]12[CH2:24][CH2:23][C:18]3([O:22][CH2:21][CH2:20][O:19]3)[CH2:17][CH:4]1[CH2:5][CH2:6][O:7][C:8]1[C:9]2=[CH:10][C:11]2[CH:12]=[N:13][NH:14][C:15]=2[CH:16]=1)[CH3:2].I[C:26]1[CH:31]=[CH:30][N:29]=[C:28]([CH3:32])[CH:27]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[C@@H]1(N)CCCC[C@H]1N>O1CCOCC1.[Cu]I>[CH2:1]([C:3]12[CH2:24][CH2:23][C:18]3([O:22][CH2:21][CH2:20][O:19]3)[CH2:17][CH:4]1[CH2:5][CH2:6][O:7][C:8]1[C:9]2=[CH:10][C:11]2[CH:12]=[N:13][N:14]([C:26]3[CH:31]=[CH:30][N:29]=[C:28]([CH3:32])[CH:27]=3)[C:15]=2[CH:16]=1)[CH3:2]

Participants

7

Reactant 4

HCID 438061,2-Diaminocyclohexane, trans-HCID 62657Potassium Phosphate, TribasicHCID 126913224-Iodo-2-methylpyridineHCID 86722439HCID 86722439, compound

Product 1

HCID 86722438HCID 86722438, compoundYield 87%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Procedure

A 25 mL round-bottom flask equipped with air cooled reflux condenser was charged with rac-(4aR,12bS)-12b-ethyl-1,2,4,4a,5,6,9,12b-octahydro spiro[benzo[4,5]oxepino[3,2-f]indazole-3,2′-[1,3]dioxolane] (90, R2=Ethyl) (1.00 g, 3.05 mmol), 4-iodo-2-methylpyridine (prepared as described in US 20070287708; 1.19 g, 4.57 mmol), CuI (0.058 g, 0.30 mmol), K3PO4 (1.29 g, 6.09 mmol) and (+/−)-trans-cyclohexane-1,2-diamine (0.070 g, 0.61 mmol) in dioxane (7.5 mL). The reaction mixture was heated at reflux in a heating block for about 18 h. The reaction mixture was filtered through a pad of Celite® using washes of EtOAc (2×20 mL). The filtrate was concentrated under reduced pressure and the residue was purified on silica gel (40 g, eluted with 0% to 100% EtOAc in DCM). Collection and concentration of the appropriate fractions gave rac-(4aR,12bS)-12b-ethyl-9-(2-methylpyridin-4-yl)-1,2,4,4a,5,6,9,12b-octahydrospiro[benzo[4,5]oxepino[3,2-f]indazole-3,2′-[1,3]dioxolane] (91, R1=2-methylpyridin-4-yl, R2=Ethyl) (1.11 g, 87%). LC/MS, method 3, Rt=2.47 min, MS m/z 420 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 8.57 (d, J=5.9 Hz, 1H), 8.19 (s, 1H), 7.86-7.70 (m, 2H), 7.65 (s, 1H), 7.53 (s, 1H), 4.39-4.30 (m, 1H), 4.01-3.85 (m, 4H), 3.82-3.70 (m, 1H), 2.87-2.68 (m, 4H), 2.50-2.40 (m, 1H), 2.32-2.21 (m, 2H), 2.03-1.32 (m, 7H), (t, J=7.4 Hz, 3H).

Workup

  1. customA 25 mL round-bottom flask equipped with air
  2. temperaturecooled
  3. temperaturereflux condenser
  4. temperatureThe reaction mixture was heated
  5. temperatureat reflux in a heating block for about 18 h
  6. filtrationThe reaction mixture was filtered through a pad of Celite®
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customthe residue was purified on silica gel (40 g, eluted with 0% to 100% EtOAc in DCM)
  9. customCollection and concentration of the appropriate fractions

Sources & evidence

ORD record
ord-51dc8aeb48d94b59941e2833315ad7a4
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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