4-Methylmorpholine → 4-{2-Chloro-1-[2-(3-methoxy-propoxy)-phenyl]-1h-indole-3-carbonyl}-piperazine-1-carboxylic acid tert-butyl ester

HRID 1510075Notes

Reaction equation

HRID 1510075 reaction equation
[Cl:1][C:2]1[N:3]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[O:20][CH2:21][CH2:22][CH2:23][O:24][CH3:25])[C:4]2[C:9]([C:10]=1[C:11]([OH:13])=O)=[CH:8][CH:7]=[CH:6][CH:5]=2.CN1CCOCC1.F[B-](F)(F)F.C(OC(C(=NOC(N(C)C)=[N+](C)C)C#N)=O)C.[N:55]1([C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])[CH2:60][CH2:59][NH:58][CH2:57][CH2:56]1>CN(C=O)C>[C:64]([O:63][C:61]([N:55]1[CH2:60][CH2:59][N:58]([C:11]([C:10]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[N:3]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[O:20][CH2:21][CH2:22][CH2:23][O:24][CH3:25])[C:2]=2[Cl:1])=[O:13])[CH2:57][CH2:56]1)=[O:62])([CH3:67])([CH3:65])[CH3:66]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 2733286O-[(Ethoxycarbonyl)cyanomethylenamino]-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 669203792-Chloro-1-[2-(3-methoxy-propoxy)-phenyl]-1h-indole-3-carboxylic acid

Product 1

HCID 669204574-{2-Chloro-1-[2-(3-methoxy-propoxy)-phenyl]-1h-indole-3-carbonyl}-piperazine-1-carboxylic acid tert-butyl esterYield 97.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 200 mg (556 μmol) of the compound of step 5 in DMF (5 ml) and NMM (122 μl, 1.11 mmol) was added O-[(ethoxycarbonyl)cyanomethyleneamino]-N,N,N′,N′-tetramethyluronium tetrafluoroborate (201 mg, 612 μmol), and the mixture was stirred at room temperature for 30 min. tert-Butyl 1-piperazinecarboxylate (114 mg, 612 μmol) was then added and the reaction mixture was stirred for 3 h. The mixture was quenched with water and extracted with EA. The organic layer was separated, dried over sodium sulfate, filtered, and evaporated. The residue was purified by silica gel chromatography (EA/HEP 2:5). 285 mg of the title compound were obtained.

Workup

  1. additionwas then added
  2. customThe mixture was quenched with water
  3. extractionextracted with EA
  4. customThe organic layer was separated
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by silica gel chromatography (EA/HEP 2:5)

Sources & evidence

ORD record
ord-3fae22b3fae542aab00a020d97d4c16f
Source dataset
uspto-grants-2012_07
Patent number
US08211885B2

Reaction notes

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