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

HRID 855350Notes

Reaction equation

HRID 855350 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:11]([OH:13])=O)[CH:10]=1)[NH:7][CH:6]=[CH:5]2.[CH2:14]([O:21][C:22]1[CH:23]=[C:24]([CH2:28][CH2:29][NH:30][CH2:31][C:32]2[CH:37]=[CH:36][C:35]([C:38]([CH3:41])([CH3:40])[CH3:39])=[CH:34][CH:33]=2)[CH:25]=[CH:26][CH:27]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.CN1CCOCC1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C.O>[CH2:14]([O:21][C:22]1[CH:23]=[C:24]([CH2:28][CH2:29][N:30]([CH2:31][C:32]2[CH:37]=[CH:36][C:35]([C:38]([CH3:41])([CH3:40])[CH3:39])=[CH:34][CH:33]=2)[C:11]([C:9]2[CH:10]=[C:2]([Cl:1])[CH:3]=[C:4]3[C:8]=2[NH:7][CH:6]=[CH:5]3)=[O:13])[CH:25]=[CH:26][CH:27]=1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 668685635-chloro-1H-indole-7-carboxylic acidHCID 68562248[2-(3-Benzyloxy-phenyl)-ethyl]-(4-tert-butyl-benzyl)-amine

Product 1

HCID 866030545-chloro-1H-indole-7-carboxylic acid [2-(3-benzyloxy-phenyl)-ethyl]-(4-tert-butyl-benzyl)-amideYield 90%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 951 mg (4.86 mmol) of 5-chloro-1H-indole-7-carboxylic acid and 1.997 g (5.35 mmol) [2-(3-benzyloxy-phenyl)-ethyl]-(4-tert-butyl-benzyl)-amine in 50 ml DMF, were added 1.6 ml (14.58 mmol) N-methylmorpholine and 2.77 g TBTU (7.29 mmol) at rt. After stirring for 16 h at rt, the reaction mixture was diluted with 300 ml water and extracted with EtOAc (2×). The combined organic phases were washed with twice 200 ml water and 100 ml brine, dried with magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography (90 g silica gel; heptane/EtOAc 9:1 then 4:1) to give 2.41 g of 5-chloro-1H-indole-7-carboxylic acid [2-(3-benzyloxy-phenyl)-ethyl]-(4-tert-butyl-benzyl)-amide as a light yellow solid (88%). MS (ISP) 551.3 (M+H)+.

Workup

  1. extractionextracted with EtOAc (2×)
  2. washThe combined organic phases were washed with twice 200 ml water and 100 ml brine
  3. dry with materialdried with magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography (90 g silica gel

Sources & evidence

ORD record
ord-0b2cc513c2e645a197ad1325132743f1
Source dataset
uspto-grants-2007_08
Patent number
US07259183B2

Reaction notes

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