5-Methoxyindole-2-carboxylic acid → N-({4-Chloro-3-[(3-chloro-5-cyanophenyl)oxy]phenyl}methyl)-5-(methyloxy)-1H-indole-2-carboxamide

HRID 1874772Notes

Reaction equation

HRID 1874772 reaction equation
[NH2:1][CH2:2][C:3]1[CH:4]=[CH:5][C:6]([Cl:19])=[C:7]([O:9][C:10]2[CH:11]=[C:12]([CH:15]=[C:16]([Cl:18])[CH:17]=2)[C:13]#[N:14])[CH:8]=1.[CH3:20][O:21][C:22]1[CH:23]=[C:24]2[C:28](=[CH:29][CH:30]=1)[NH:27][C:26]([C:31](O)=[O:32])=[CH:25]2.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[Cl:19][C:6]1[CH:5]=[CH:4][C:3]([CH2:2][NH:1][C:31]([C:26]2[NH:27][C:28]3[C:24]([CH:25]=2)=[CH:23][C:22]([O:21][CH3:20])=[CH:30][CH:29]=3)=[O:32])=[CH:8][C:7]=1[O:9][C:10]1[CH:11]=[C:12]([C:13]#[N:14])[CH:15]=[C:16]([Cl:18])[CH:17]=1

Participants

6

Reactant 4

HCID 204015-Methoxyindole-2-carboxylic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 594514053-{[5-(Aminomethyl)-2-chlorophenyl]oxy}-5-chlorobenzonitrile

Product 1

HCID 59451352N-({4-Chloro-3-[(3-chloro-5-cyanophenyl)oxy]phenyl}methyl)-5-(methyloxy)-1H-indole-2-carboxamideYield 37.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-({4-Chloro-3-[(3-chloro-5-cyanophenyl)oxy]phenyl}methyl)-5-(methyloxy)-1H-indole-2-carboxamide was prepared in a similar manner as described herein from 3-{[5-(aminomethyl)-2-chlorophenyl]oxy}-5-chlorobenzonitrile (0.025 g, 0.085 mmol), 5-(methyloxy)-1H-indole-2-carboxylic acid, (0.025 g, 0.13 mmol), HATU (0.05 g, 0.13 mmol), DIPEA (0.025 mL, 0.13 mmol) and DMF (1 mL). The crude material was purified by Reverse-Phase HPLC (water/acetonitrile with 0.1% TFA). The desired fractions were neutralized and extracted with EtOAc. The organic extracts were combined, dried over Na2SO4, filtered and evaporated to afford the title compound (0.015 g, 36%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 11.42 (d, 1H), 8.98 (t, 1H), 7.76 (d, 1H), 7.59 (d, 1H), 7.43 (dd, 1H), 7.35 (d, 1H), 7.25-7.28 (m, 2H), 7.23 (d, 1H), 7.03 (dd, 2H), 6.80 (dd, 1H), 4.48 (d, 2H), 3.72 (s, 3H). MS: m/z 466.1 (M+1).

Workup

  1. customN-({4-Chloro-3-[(3-chloro-5-cyanophenyl)oxy]phenyl}methyl)-5-(methyloxy)-1H-indole-2-carboxamide was prepared in a similar manner
  2. customThe crude material was purified by Reverse-Phase HPLC (water/acetonitrile with 0.1% TFA)
  3. extractionextracted with EtOAc
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-7ca2c8f6246f45508fe4881e4d3def4e
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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