Pyridine → HCID 59837417, compound

HRID 273022Notes

Reaction equation

HRID 273022 reaction equation
[CH3:1][S:2]([O:5]S(C)(=O)=O)(=O)=[O:3].[N:10]1([CH2:15][CH2:16][CH2:17][O:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]3([CH2:31][N:32]4[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]4)[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]3)=[CH:21][CH:20]=2)[CH2:14][CH2:13][CH2:12][CH2:11]1.N1C=CC=CC=1>ClCCl>[CH3:1][S:2]([N:35]1[CH2:36][CH2:37][N:32]([CH2:31][C:25]2([C:22]3[CH:21]=[CH:20][C:19]([O:18][CH2:17][CH2:16][CH2:15][N:10]4[CH2:11][CH2:12][CH2:13][CH2:14]4)=[CH:24][CH:23]=3)[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30]2)[CH2:33][CH2:34]1)(=[O:5])=[O:3]

Participants

5

Reactant 3

HCID 1049PyridineHCID 81560Methanesulfonic anhydrideHCID 59837511HCID 59837511, compound

Product 1

HCID 59837417HCID 59837417, compoundYield 57.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Methanesulphonic acid anhydride (49 mg, 0.28 mmol) was added at 0° C. to a solution of 1-({1-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]cyclohexyl}methyl) piperazine (90 mg, 0.23 mmol) and pyridine (47 μl, 0.58 mmol) in dichloromethane (1 ml). The reaction was stirred at 0° C. for 10 minutes, then allowed to warm up to room temperature and stirred for 18 hours. The reaction mixture was concentrated under reduced pressure and partitioned between dichloromethane (20 ml) and aqueous sodium carbonate (20 ml). The layers were separated. The organic layer was dried over sodium sulphate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (96:4:0.4 by volume) to provide the title compound (61 mg, 56%). 1H NMR (400 MHz, CDCl3) δ 1.29-1.36 (m, 3H), 1.45-1.52 (m, 5H), 1.85-1.90 (m, 4H), 2.08-2.15 (m, 4H), 2.22 (t, 4H), 2.32 (s, 2H), 2.67-2.79 (m, 9H), 3.00-3.03 (m, 4H), 4.02 (t, 2H), 6.83 (d, 2H), 7.24 (d, 2H). HRMS ESI+ m/z 464.2931 [MH]+.

Workup

  1. temperatureto warm up to room temperature
  2. stirringstirred for 18 hours
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. custompartitioned between dichloromethane (20 ml) and aqueous sodium carbonate (20 ml)
  5. customThe layers were separated
  6. dry with materialThe organic layer was dried over sodium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (96:4:0.4 by volume)

Sources & evidence

ORD record
ord-526b33eee82247a49cc3afb86fbf0840
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

Loading…