Diisopropylethylamine → N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]phenyl}methyl)-6-(methyloxy)-1H-indole-3-carboxamide

HRID 1874767Notes

Reaction equation

HRID 1874767 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:30]=[C:29]2[C:25]([C:26]([C:31](O)=[O:32])=[CH:27][NH:28]2)=[CH:24][CH:23]=1.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.C(#N)C>[Cl:19][C:6]1[CH:5]=[CH:4][C:3]([CH2:2][NH:1][C:31]([C:26]2[C:25]3[C:29](=[CH:30][C:22]([O:21][CH3:20])=[CH:23][CH:24]=3)[NH:28][CH:27]=2)=[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

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 177509566-Methoxy-1H-indole-3-carboxylic acidHCID 594514053-{[5-(Aminomethyl)-2-chlorophenyl]oxy}-5-chlorobenzonitrile

Product 1

HCID 59451549N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]phenyl}methyl)-6-(methyloxy)-1H-indole-3-carboxamideYield 75.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

N-({4-Chloro-3-[(3-chloro-5-cyanophenyl)oxy]phenyl}methyl)-6-(methyloxy)-1H-indole-3-carboxamide was prepared in a similar manner as described herein from 3-{[5-(aminomethyl)-2-chlorophenyl]oxy}-5-chlorobenzonitrile (0.05 g, 0.17 mmol), 6-(methyloxy)-1H-indole-3-carboxylic acid, (0.035 g, 0.18 mmol), HATU (0.1 g, 0.25 mmol), DIPEA (0.05 mL, 0.25 mmol), acetonitrile (3 mL) 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 (0.06 g, 75%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 11.33 (br. s., 1H), 8.39 (s, 1H), 7.93 (d, 1H), 7.86 (d, 1H), 7.77 (d, 1H), 7.58 (d, 1H), 7.43 (dd, 1H), 7.34 (t, 1H), 7.27 (dd, 1H), 7.22 (d, 1H), 6.88 (d, 1H), 6.71 (dd, 1H), 4.43 (d, 2H), 3.74 (s, 3H). MS: m/z 466.0 (M+1).

Workup

  1. customN-({4-Chloro-3-[(3-chloro-5-cyanophenyl)oxy]phenyl}methyl)-6-(methyloxy)-1H-indole-3-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-ee8bf5f7521f4a1996df59be3906af95
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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