Potassium Carbonate → HCID 59730068, compound

HRID 228335Notes

Reaction equation

HRID 228335 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]1[NH:8][CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1.Cl[C:19]1[CH:27]=[CH:26][C:22]([C:23]([NH2:25])=[O:24])=[CH:21][N:20]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.C1(C)C=CC=CC=1>[OH:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]1[NH:8][CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][C:19]2[CH:27]=[CH:26][C:22]([C:23]([NH2:25])=[O:24])=[CH:21][N:20]=2)=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 804566-ChloronicotinamideHCID 59730384HCID 59730384, compound

Product 1

HCID 59730068HCID 59730068, compound

Reagents, catalysts & solvents 1

HCID 21735183Dimethylformamide tolueneSolvent

Procedure

Heat a mixture of 4-[2-(2-hydroxycyclohexylamino)ethyl]phenol (152.6 mg, 0.65 mmol), 6-chloronicotinamide (84.6 mg, 0.54 mmol) and K2CO3 (186.7 mg, 1.35 mmol) in 3:1 DMF/toluene (4.0 mL) at 160° C. for 2 hours. Cool to room temperature and filter with thorough MeOH and CH2Cl2 wash. Concentrate the filtrate and remove DMF azeotropically with xylenes. Purify by flash chromatography, eluting with 75:15:10 EtOAc/CH2Cl2/2.0 M NH3 in MeOH (56.3 mg, 29%): MS ES+ 356.1 (M+H)+, HRMS calcd for C20H26N3O3 356.1974 (M+H)+, found 356.1966, time 0.37 min; HPLC [YMC-Pack Pro C-18 (150×4.6 mm, S-5 microm), acetonitrile in water containing 0.01% concentrated HCl at 1.0 mL/min, 30-99% over 19 min], tR=1.23 min, 100% purity; Chiralpak AD 225 nm, 60:40 EtOH/heptane at 1.0 mL/min, tR=5.55 min, 50% and tR=7.17 min, 50%; Anal. Calcd for C20H25N3O3.0.2CH2Cl2.0.2MeOH: C, 64.68; H, 6.97; N, 11.09. Found: C, 64.46; H, 6.84; N, 11.11.

Workup

  1. temperatureHeat
  2. filtrationfilter with thorough MeOH and CH2Cl2
  3. washwash
  4. concentrationConcentrate the filtrate
  5. customremove DMF azeotropically with xylenes
  6. customPurify by flash chromatography
  7. washeluting with 75:15:10 EtOAc/CH2Cl2/2.0 M NH3 in MeOH (56.3 mg, 29%)
  8. custom356.1966, time 0.37 min
  9. customHPLC [YMC-Pack Pro C-18 (150×4.6 mm, S-5 microm), acetonitrile in water containing 0.01% concentrated HCl at 1.0 mL/min, 30-99% over 19 min], tR=1.23 min, 100% purity

Sources & evidence

ORD record
ord-7244f4d6a2ef4f8b9973bc4b901e49d7
Source dataset
uspto-grants-2009_07
Patent number
US07560463B2

Reaction notes

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