Methanol → N-(2-Amino-phenyl)-3-[4-({(2-hydroxy-ethyl)-[2-(1H-indol-3-yl)-ethyl]-amino}-methyl)-phenyl]-acrylamide

HRID 416211Notes

Reaction equation

HRID 416211 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:41])[CH:10]=[CH:11][C:12]1[CH:17]=[CH:16][C:15]([CH2:18][N:19]([CH2:31][CH2:32][O:33][Si](C(C)(C)C)(C)C)[CH2:20][CH2:21][C:22]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[NH:24][CH:23]=2)=[CH:14][CH:13]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-].CO>C1COCC1>[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:41])[CH:10]=[CH:11][C:12]1[CH:13]=[CH:14][C:15]([CH2:18][N:19]([CH2:31][CH2:32][OH:33])[CH2:20][CH2:21][C:22]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[NH:24][CH:23]=2)=[CH:16][CH:17]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 2724141Tetrabutylammonium FluorideHCID 66621918N-(2-Amino-phenyl)-3-[4-({[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-[2-(1H-indol-3-yl)-ethyl]-amino}-methyl)-phenyl]-acrylamide

Product 1

HCID 66622582N-(2-Amino-phenyl)-3-[4-({(2-hydroxy-ethyl)-[2-(1H-indol-3-yl)-ethyl]-amino}-methyl)-phenyl]-acrylamideYield 80.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution at −20° C. of 5 (1.49 g, 2.62 mmol) in anhydrous THF (30 mL) under nitrogen was slowly added a solution of TBAF (2.88 mL, 2.88 mmol, 1.0M in THF). The reaction mixture was allowed to warm-up to the room temperature over 1 h and was stirred for additional 22 hours. MeOH was added and the reaction mixture was concentrated, diluted with AcOEt, and successively washed with saturated aqueous solution of NaHCO3, H2O, a saturated aqueous solution of NH4Cl and brine, dried over MgSO4, filtered, and concentrated. The residue was purified by flash chromatography on silica gel (MeOH/CH2Cl2, 5/95→10/90 plus several drops of NH4OH) and triturated with a mixture of AcOEt/CH2Cl2/hexane to afford the title compound 6 (956 mg, 2.10 mmol, 80% yield) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) δ(ppm): 10.76 (s, 1H), 9.39 (s, 1H), AB system (δA=7.58, δB=7.44, JAB=8.0 Hz, 4H), 7.56 (d, J=15.7 Hz, 1H), 7.42-7.34 (m, 2H), 7.33 (d, J=8.0 Hz, 1H), 7.12 (d, J=2.3 Hz, 1H), 7.05 (td, J=7.2, 1.2 Hz, 1H), 6.98-6.90 (m, 2H), 6.90 (d, J=15.8 Hz, 1H), 6.77 (dd, J=8.0, 1.4 Hz, 1H), 6.60 (ddd, J=7.5, 7.5, 1.4 Hz, 1H), 4.98 (bs, 2H), 4.43 (t, J=5.4 Hz, 1H), 3.78 (s, 2H), 3.56 (td, J=6.3, 5.6 Hz, 2H), 2.94-2.84 (m, 2H), 2.82-2.74 (m, 2H), 2.68 (t, J=6.5 Hz, 2H).

Workup

  1. concentrationthe reaction mixture was concentrated
  2. additiondiluted with AcOEt
  3. washsuccessively washed with saturated aqueous solution of NaHCO3, H2O
  4. dry with materiala saturated aqueous solution of NH4Cl and brine, dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography on silica gel (MeOH/CH2Cl2, 5/95→10/90 plus several drops of NH4OH)
  8. customtriturated with a mixture of AcOEt/CH2Cl2/hexane

Sources & evidence

ORD record
ord-ca4555ee1cb84bc7a76d51da3988d2fe
Source dataset
uspto-grants-2012_01
Patent number
US08088805B2

Reaction notes

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