1,1'-Carbonyldiimidazole → HCID 57619816, compound

HRID 1642477Notes

Reaction equation

HRID 1642477 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][CH:9]1[CH2:14][CH2:13][N:12]([C:15]2([CH3:28])[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]2)[CH2:11][CH2:10]1.[C:29](N1C=CN=C1)(N1C=CN=C1)=[O:30]>C(#N)C>[O:30]=[C:29]1[N:8]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]3([CH3:28])[CH2:16][CH2:17][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:19][CH2:20]3)[CH2:11][CH2:10]2)[C@H:3]2[CH2:4][CH2:5][CH2:6][CH2:7][C@@H:2]2[NH:1]1

Participants

4

Reactant 2

HCID 682631,1'-CarbonyldiimidazoleHCID 57619817HCID 57619817, compound

Product 1

HCID 57619816HCID 57619816, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of tert-butyl 4-[4-[[(1R,2R)-2-aminocyclohexyl]amino]-1-piperidyl]-4-methyl-piperidine-1-carboxylate in acetonitrile (20 mL) was added with 1,1′-carbonyldiimidazole (1.30 g, 8.0 mmol) and the reaction mixture was stirred at room temperature for 12 h. The solvent was removed in vacuo and the residue was taken up in water (20 mL) and dichloromethane (80 mL). The phases were separated and the aqueous phase was extracted with dichloromethane (2×50 mL). The combined organic phases were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to give the crude product, which was purified with preparative LC/MS (high pH) to give the title compound as white solid (849 mg, 30% over two steps). 1H NMR (400 MHz, METHANOL-D4) δ ppm 0.95 (s, 3H), 1.31-1.40 (m, 4H), 1.42 (s, 9H), 1.44-1.48 (m, 2H), 1.52-1.63 (m, 1H), 1.64-1.89 (m, 8H), 1.93-1.99 (m, 1H), 2.08-2.21 (m, 2H), 2.25-2.32 (m, 1H), 2.89-3.10 (m, 4H), 3.28-3.36 (m, 1H), 3.42-3.53 (m, 2H), 3.54-3.65 (m, 1H). MS (M+1): 421.3.

Workup

  1. customThe solvent was removed in vacuo
  2. customThe phases were separated
  3. extractionthe aqueous phase was extracted with dichloromethane (2×50 mL)
  4. washThe combined organic phases were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give the crude product, which
  9. customwas purified with preparative LC/MS (high pH)

Sources & evidence

ORD record
ord-ce068dc63d634dd1958855b991e1b748
Source dataset
uspto-grants-2012_02
Patent number
US08119661B2

Reaction notes

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