Cesium carbonate → HCID 178513952, compound

HRID 518777Notes

Reaction equation

HRID 518777 reaction equation
Cl[C:2]1[CH:7]=[C:6]([NH:8][C@H:9]2[CH2:14][CH2:13][C@H:12]([C:15]([NH2:17])=[O:16])[CH2:11][CH2:10]2)[C:5]([N+:18]([O-:20])=[O:19])=[CH:4][N:3]=1.[N:21]1([CH2:27][CH2:28][OH:29])[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1.C1OCCOCCOCCOCCOCCOC1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C(Cl)Cl>[N+:18]([C:5]1[C:6]([NH:8][C@H:9]2[CH2:14][CH2:13][C@H:12]([C:15]([NH2:17])=[O:16])[CH2:11][CH2:10]2)=[CH:7][C:2]([O:29][CH2:28][CH2:27][N:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)=[N:3][CH:4]=1)([O-:20])=[O:19]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 18232N-PiperidinoethanolHCID 2855718-Crown-6HCID 178513949HCID 178513949, compound

Product 1

HCID 178513952HCID 178513952, compoundYield 41.2%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
80 °C

Procedure

Trans-4-(2-Chloro-5-nitropyridin-4-ylamino)cyclohexanecarboxamide (3.00 g, 10.04 mmol) was suspended in toluene (30 mL). 1-Piperidine ethanol (6.62 mL, 50.2 mmol), 18-crown-6 (3.98 g, 15.06 mmol) and cesium carbonate (9.82 g, 30.1 mmol) were then added to the reaction. The resulting reaction mixture was heated at 80° C. overnight followed by additional heating at 90° C. for 8 hours. The reaction mixture was diluted with DCM and washed with water and brine. The organic layer was concentrated under vacuum to yield 6.43 g of crude material as a yellow oil/residue. The sample was purified by flash chromatography, eluting with 0-100% 90:10:1 dichloromethane/methanol/NH4OH:dichloromethane to afford 1.62 g of trans-4-(5-nitro-2-(2-(piperidin-1-yl)ethoxy)pyridin-4-ylamino)cyclohexanecarboxamide (41.2% yield) as a yellow solid. Mass cal'd: 391.2; MS (ESI pos. ion) m/z: 392.2 [M+H].

Workup

  1. customThe resulting reaction mixture
  2. temperatureby additional heating at 90° C. for 8 hours
  3. washwashed with water and brine
  4. concentrationThe organic layer was concentrated under vacuum
  5. customto yield 6.43 g of crude material as a yellow oil/residue
  6. customThe sample was purified by flash chromatography
  7. washeluting with 0-100% 90:10:1 dichloromethane/methanol/NH4OH

Sources & evidence

ORD record
ord-fd52e2fd8df54ed39e8b325c18325515
Source dataset
uspto-grants-2015_08
Patent number
US09115127B2

Reaction notes

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