2,6-Lutidine → HCID 66551445, compound

HRID 922412Notes

Reaction equation

HRID 922412 reaction equation
[Cl:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([C@H:11]([N:13]([CH:36]3[CH2:38][CH2:37]3)[C:14]([C@H:16]3[CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19][CH2:18][N:17]3C(OC(C)(C)C)=O)=[O:15])[CH3:12])=[CH:8][CH:9]=2)[N:4]([CH2:39][CH2:40][CH2:41][O:42][CH3:43])[CH:3]=1.N1C(C)=CC=CC=1C.C[Si](OS(C(F)(F)F)(=O)=O)(C)C.C(=O)([O-])O.[Na+]>ClCCl.CO>[Cl:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([C@H:11]([N:13]([CH:36]3[CH2:38][CH2:37]3)[C:14]([C@H:16]3[CH2:21][NH:20][CH2:19][CH2:18][NH:17]3)=[O:15])[CH3:12])=[CH:8][CH:9]=2)[N:4]([CH2:39][CH2:40][CH2:41][O:42][CH3:43])[CH:3]=1

Participants

7

Reactant 4

HCID 79372,6-LutidineHCID 65367Trimethylsilyl triflateHCID 516892Sodium BicarbonateHCID 68308649HCID 68308649, compound

Product 1

HCID 66551445HCID 66551445, compoundYield 85.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of di-tert-butyl (2R)-2-{[{(1R)-1-[3-chloro-1-(3-methoxypropyl)-1H-indol-6-yl]ethyl}(cyclopropyl)amino]carbonyl}piperazine-1,4-dicarboxylate (44.0 mg) and 2,6-lutidine (0.050 mL) in dichloromethane (1.0 mL) was added trimethylsilyltriflate (0.051 mL) under ice-cooling, and the mixture was stirred at the same temperature for 1 hour. Then, thereto were added aqueous saturated sodium hydrogen carbonate solution and methanol (2.0 mL) under ice-cooling, and the mixture was extracted with chloroform. The organic layer was washed with saturated saline, dried over magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by NH-silica gel column chromatography (eluent: ethyl acetate→ethyl acetate/methanol=5/1) to give (2R)-N-{(1R)-1-[3-chloro-1-(3-methoxypropyl)-1H-indol-6-yl]ethyl}-N-cyclopropylpiperazine-2-carboxamide [Ex(2-1)] (25.4 mg) and as a colorless oil.

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. extractionthe mixture was extracted with chloroform
  4. washThe organic layer was washed with saturated saline
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by NH-silica gel column chromatography (eluent: ethyl acetate→ethyl acetate/methanol=5/1)

Sources & evidence

ORD record
ord-86e10ee712c540bd967472fbdaa8f411
Source dataset
uspto-grants-2016_03
Patent number
US09278944B2

Reaction notes

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