2-Aminoadamantane hydrochloride → HCID 66954042, compound

HRID 1424632Notes

Reaction equation

HRID 1424632 reaction equation
Cl.[NH2:2][CH:3]1[CH:10]2[CH2:11][CH:6]3[CH2:7][CH:8]([CH2:12][CH:4]1[CH2:5]3)[CH2:9]2.CCN(C(C)C)C(C)C.C1N=CN([C:27]([N:29]2[CH:33]=N[CH:31]=[CH:30]2)=[O:28])C=1.[Br:34][C:35]1[CH:36]=[CH:37][CH:38]=[C:39]2[C:48]=1[C:42]1(CCNC[CH2:43]1)[CH2:41][C:40]2=[CH:49][C:50]([O:52][CH2:53][CH3:54])=[O:51]>C(Cl)Cl>[Br:34][C:35]1[CH:36]=[CH:37][CH:38]=[C:39]2[C:48]=1[C:42]1([CH2:31][CH2:30][N:29]([C:27](=[O:28])[NH:2][CH:3]3[CH:4]4[CH2:12][CH:8]5[CH2:7][CH:6]([CH2:11][CH:10]3[CH2:9]5)[CH2:5]4)[CH2:33][CH2:43]1)[CH2:41][C:40]2=[CH:49][C:50]([O:52][CH2:53][CH3:54])=[O:51]

Participants

6

Reactant 4

HCID 253312-Aminoadamantane hydrochlorideHCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 66953637HCID 66953637, compound

Product 1

HCID 66954042HCID 66954042, compoundYield 35.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 2-aminoadamantane hydrochloride (4.17 g, 22 mmol) and DIEA (28.7 g, 223 mmol) in anhydrous CH2Cl2 (40 mL) was added CDI (4.33 g, 27 mmol) at 0° C. and then stirred for 1 h at 0° C. under N2 atmosphere. Ethyl 2-(7-bromospiro[indene-1,4′-piperidine]-3(2H)-ylidene)acetate (7.77 g, 22 mmol) in CH2Cl2 anhydrous (40 mL) was added dropwise to the above mixture. The mixture was stirred for 8 h at rt under N2. The reaction mixture was washed with 1 N aq HCl. The organic layer was dried over Na2SO4, filtered and concentrated to leave a residue, which was purified by silica gel column chromatography to afford ethyl 2-(7-bromo-1′-(2-adamantylcarbamoyl)spiro[indene-1,4′-piperidine]-3(2H)-ylidene)acetate (4.1 g, 35%). Preparative SFC using a ChiralCel-OJ, 400×25 mm I.D, 20 μm (Daicel Chemical Industries, Ltd) column maintained at 35° C. eluted with 75:25 supercritical CO2/MeOH at a flow rate of 70 mL min−1 and a nozzle pressure of 100 bar afforded two isomers.

Workup

  1. stirringThe mixture was stirred for 8 h at rt under N2
  2. washThe reaction mixture was washed with 1 N aq HCl
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto leave a residue, which
  7. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-f5d3d1ee9fa64c6aa587599688c8407f
Source dataset
uspto-grants-2015_01
Patent number
US08927715B2

Reaction notes

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