O-Phenylenediamine → N-(2-Amino-phenyl)-3-[4-({[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-[2-(1H-indol-3-yl)-ethyl]-amino}-methyl)-phenyl]-acrylamide

HRID 416210Notes

Reaction equation

HRID 416210 reaction equation
[C:1]([Si:5]([CH3:34])([CH3:33])[O:6][CH2:7][CH2:8][N:9]([CH2:21][C:22]1[CH:27]=[CH:26][C:25]([CH:28]=[CH:29][C:30]([OH:32])=O)=[CH:24][CH:23]=1)[CH2:10][CH2:11][C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[NH:14][CH:13]=1)([CH3:4])([CH3:3])[CH3:2].CCN(CC)CC.CN([P+](O[N:53]1N=[N:60][C:55]2[CH:56]=[CH:57][CH:58]=[CH:59][C:54]1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.C1(N)C=CC=CC=1N.[NH4+].[Cl-]>CN(C=O)C>[NH2:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][C:55]=1[NH:60][C:30](=[O:32])[CH:29]=[CH:28][C:25]1[CH:26]=[CH:27][C:22]([CH2:21][N:9]([CH2:8][CH2:7][O:6][Si:5]([C:1]([CH3:2])([CH3:4])[CH3:3])([CH3:34])[CH3:33])[CH2:10][CH2:11][C:12]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[NH:14][CH:13]=2)=[CH:23][CH:24]=1

Participants

7

Reactant 5

HCID 7243O-PhenylenediamineHCID 8471Triethylamine2×HCID 25517Ammonium ChlorideHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 666223893-[4-({[2-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-[2-(1H-indol-3-yl)ethyl]-amino}-methyl)-phenyl]-acrylic acid

Product 1

HCID 66621918N-(2-Amino-phenyl)-3-[4-({[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-[2-(1H-indol-3-yl)-ethyl]-amino}-methyl)-phenyl]-acrylamideYield 96.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirred solution of 4 (1.30 g, 2.72 mmol) in anhydrous DMF (20 mL) at room temperature under nitrogen were added Et3N (330 μl, 3.26 mmol) and BOP reagent (1.32 g, 2.99 mmol), respectively. After 30 min, a solution of 1,2-phenylenediamine (352 mg, 3.26 mmol), Et3N (1.14 mL, 8.15 mmol) in anhydrous DMF (3 mL) was added dropwise. After 3 h the reaction mixture was poured into saturated aqueous solution of NH4Cl, and extracted with AcOEt. The extract was washed with saturated NH4Cl, water and brine, dried over MgSO4, filtered, concentrated and purified by flash chromatography on silica gel (MeOH/CH2Cl2, 5/95 plus several drops of NH4OH), to afford the title compound 5 (1.49 g, 2.62 mmol, 96% yield) as a yellow sticky foam. 1H NMR (300 MHz, DMSO-d6) δ(ppm): 10.78 (s, 1H), 9.40 (s, 1H), 7.59 (d, J=8.0 Hz, 2H), 7.58 (d, J=15.8 Hz, 1H), 7.45 (d, J=7.9 Hz, 2H), 7.40 (t, J=7.7 Hz, 2H), 7.35 (d, J=8.4 Hz, 1H), 7.14 (s, 1H), 7.07 (t, J=7.5 Hz, 1H), 7.05-6.85 (m, 3H), 6.79 (d, J=7.9 Hz, 1H), 6.62 (t, J=7.5 Hz, 1H), 4.98 (bs, 2H), 3.80 (s, 2H), 3.71 (t, J=6.2 Hz, 2H), 2.95-2.75 (m, 4H), 2.71 (t, J=6.2 Hz, 2H), 0.89 (s, 9H), 0.05 (s, 6H).

Workup

  1. extractionextracted with AcOEt
  2. washThe extract was washed with saturated NH4Cl, water and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by flash chromatography on silica gel (MeOH/CH2Cl2, 5/95 plus several drops of NH4OH)

Sources & evidence

ORD record
ord-e832f148225c40c5820f587773b6775d
Source dataset
uspto-grants-2012_01
Patent number
US08088805B2

Reaction notes

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