4-Methylmorpholine → 5-Chloro-1H-indole-7-carboxylic acid (4-tert-butyl-2-chloro-benzyl)-[2-(4-fluoro-phenyl)-ethyl]-amide

HRID 855454Notes

Reaction equation

HRID 855454 reaction equation
CN1CCOCC1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Cl:32][C:33]1[CH:34]=[C:35]2[C:39](=[C:40]([C:42]([OH:44])=O)[CH:41]=1)[NH:38][CH:37]=[CH:36]2.[C:45]([C:49]1[CH:65]=[CH:64][C:52]([CH2:53][NH:54][CH2:55][CH2:56][C:57]2[CH:62]=[CH:61][C:60]([F:63])=[CH:59][CH:58]=2)=[C:51]([Cl:66])[CH:50]=1)([CH3:48])([CH3:47])[CH3:46]>CN(C=O)C.O>[C:45]([C:49]1[CH:65]=[CH:64][C:52]([CH2:53][N:54]([CH2:55][CH2:56][C:57]2[CH:58]=[CH:59][C:60]([F:63])=[CH:61][CH:62]=2)[C:42]([C:40]2[CH:41]=[C:33]([Cl:32])[CH:34]=[C:35]3[C:39]=2[NH:38][CH:37]=[CH:36]3)=[O:44])=[C:51]([Cl:66])[CH:50]=1)([CH3:48])([CH3:46])[CH3:47]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 668685635-chloro-1H-indole-7-carboxylic acidHCID 69342921(4-Tert-butyl-2-chloro-benzyl)-[2-(4-fluoro-phenyl)-ethyl]-amine

Product 1

HCID 866031345-Chloro-1H-indole-7-carboxylic acid (4-tert-butyl-2-chloro-benzyl)-[2-(4-fluoro-phenyl)-ethyl]-amideYield 92%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

106 mg (1.05 mmol) of N-methyl morpholine and then 199 mg (0.53 mmol) of HBTU were added to 68 mg (0.35 mol) of 5-chloro-1H-indol-7-carboxylic acid and 136 mg (0.39 mmol) of (4-tert-butyl-2-chloro-benzyl)-[2-(4-fluoro-phenyl)-ethyl]-amine dissolved in 3.5 ml DMF at rt under nitrogen. The reaction mixture was stirred at rt for 3 h. Water was added and the reaction mixture was extracted twice with EtOAc. The combined organic layers were washed once with 1N aqueous HCl solution, once with saturated aqueous NaHCO3 solution and once with saturated aqueous NaCl solution, dried over sodium sulfate, filtered and the solvent was evaporated. The residue was purified by column chromatography (20 g silica gel, heptane/EtOAc 7:3) to yield 160 mg (92%) product as a light yellow foam. MS (EI) 496.1 (M)+.

Workup

  1. extractionthe reaction mixture was extracted twice with EtOAc
  2. washThe combined organic layers were washed once with 1N aqueous HCl solution, once with saturated aqueous NaHCO3 solution and once with saturated aqueous NaCl solution
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customthe solvent was evaporated
  6. customThe residue was purified by column chromatography (20 g silica gel, heptane/EtOAc 7:3)

Sources & evidence

ORD record
ord-82e2ace2e01f49f7b9bb90b58bd64050
Source dataset
uspto-grants-2007_08
Patent number
US07259183B2

Reaction notes

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