Cesium carbonate → HCID 178457858, compound

HRID 518645Notes

Reaction equation

HRID 518645 reaction equation
[N:1]1([CH2:7][CH2:8][OH:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C1OCCOCCOCCOCCOCCOC1.Cl[C:29]1[CH:34]=[C:33]([NH:35][C@@H:36]2[CH2:41][CH2:40][C@H:39]([C:42]([NH:44][CH:45]([CH3:47])[CH3:46])=[O:43])[CH2:38][CH2:37]2)[C:32]([N+:48]([O-:50])=[O:49])=[CH:31][N:30]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CO.C1(C)C=CC=CC=1>[NH4+:1].[OH-:9].[CH:45]([NH:44][C:42]([C@H:39]1[CH2:38][CH2:37][C@@H:36]([NH:35][C:33]2[C:32]([N+:48]([O-:50])=[O:49])=[CH:31][N:30]=[C:29]([O:9][CH2:8][CH2:7][N:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)[CH:34]=2)[CH2:41][CH2:40]1)=[O:43])([CH3:47])[CH3:46]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 18232N-PiperidinoethanolHCID 2855718-Crown-6HCID 178457831HCID 178457831, compound

Product 2

HCID 14923Ammonium HydroxideHCID 178457858HCID 178457858, compoundYield 85%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
75 °C

Procedure

A round-bottom flask under nitrogen was charged with 1-piperidineethanol (19.34 mL, 147 mmol), 18-crown-6 (11.63 g, 44.0 mmol), cis-4-(2-chloro-5-nitropyridin-4-ylamino)-N-isopropylcyclohexanecarboxamide (10.00 g, 29.3 mmol), cesium carbonate (28.7 g, 88 mmol) and toluene (196 mL). The reaction mixture was purged with nitrogen and heated at 75° C. for 12 hours. The reaction mixture was diluted with EtOAc, and washed with brine, followed by saturated NH4Cl (aq). The aqueous layers were back-extracted with EtOAc, and the combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo. The residual material was purified via silica gel chromatography eluting with isocratic 90:10:1 DCM:MeOH:NH4OH, to provide cis-N-isopropyl-4-(5-nitro-2-(2-(piperidin-1-yl)ethoxy)pyridin-4-ylamino)cyclohexanecarboxamide (10.79 g, 85% yield) as a rust-colored solid, which was taken forward without further purification. MS m/z=434.2 [M+H], calc 433.54 for C22H35N5O4.

Workup

  1. customThe reaction mixture was purged with nitrogen
  2. additionThe reaction mixture was diluted with EtOAc
  3. washwashed with brine
  4. extractionThe aqueous layers were back-extracted with EtOAc
  5. dry with materialthe combined organic layers were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residual material was purified via silica gel chromatography
  9. washeluting with isocratic 90:10:1 DCM

Sources & evidence

ORD record
ord-07e47c66e29b4efca8b6b6eb34e33629
Source dataset
uspto-grants-2015_08
Patent number
US09115127B2

Reaction notes

Loading…