4-Methylmorpholine → 5-Chloro-1H-indole-7-carboxylic acid (4-tert-butyl-2-chloro-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide

HRID 855455Notes

Reaction equation

HRID 855455 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:68]=[CH:67][C:52]([CH2:53][NH:54][CH2:55][CH2:56][C:57]2[CH:62]=[CH:61][CH:60]=[C:59]([C:63]([F:66])([F:65])[F:64])[CH:58]=2)=[C:51]([Cl:69])[CH:50]=1)([CH3:48])([CH3:47])[CH3:46]>CN(C=O)C.O>[C:45]([C:49]1[CH:68]=[CH:67][C:52]([CH2:53][N:54]([CH2:55][CH2:56][C:57]2[CH:62]=[CH:61][CH:60]=[C:59]([C:63]([F:66])([F:65])[F:64])[CH:58]=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:69])[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 69341988(4-Tert-butyl-2-chloro-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amine

Product 1

HCID 866031355-Chloro-1H-indole-7-carboxylic acid (4-tert-butyl-2-chloro-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amideYield 91%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

91 mg (0.9 mmol) of N-methyl morpholine and then 170 mg (0.45 mmol) of HBTU were added to 59 mg (0.30 mol) of 5-chloro-1H-indol-7-carboxylic acid and 122 mg (0.33 mmol) of (4-tert-butyl-2-chloro-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amine dissolved in 3 ml DMF at rt under nitrogen. The reaction mixture was stirred at rt over night. 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 4:1) to yield 150 mg (91%) product as a yellow viscous oil. MS (ISP) 547.3 (M+H)+.

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 4:1)

Sources & evidence

ORD record
ord-d52ac28f33fa486398a4e536bb3295a8
Source dataset
uspto-grants-2007_08
Patent number
US07259183B2

Reaction notes

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