Tributylphosphine → 2-Methyl-3-{5-[3-(2-pyridylamino)propoxy]indolyl}propanoic acid

HRID 23980Notes

Reaction equation

HRID 23980 reaction equation
N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.[OH:19][C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][CH:28]=1)[NH:25][C:24]([CH2:29][CH:30]([CH3:35])[C:31]([O:33]C)=[O:32])=[CH:23]2.O[CH2:37][CH2:38][CH2:39][NH:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][N:42]=1.C(P(CCCC)CCCC)CCC>O1CCCC1>[CH3:35][CH:30]([CH2:29][C:24]1[NH:25][C:26]2[C:22]([CH:23]=1)=[CH:21][C:20]([O:19][CH2:37][CH2:38][CH2:39][NH:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][N:42]=1)=[CH:28][CH:27]=2)[C:31]([OH:33])=[O:32]

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 114124793-((Pyridin-2-yl)amino)propan-1-olHCID 22570322Methyl 3-(5-hydroxyindolyl)-2-methylpropanoate

Product 1

HCID 225703032-Methyl-3-{5-[3-(2-pyridylamino)propoxy]indolyl}propanoic acidYield 15.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1,1′-(Azodicarbonyl)dipiperidine (0.13 g, 0.57 mmol) was added to the solution of methyl 3-(5-hydroxyindolyl)-2-methylpropanoate (0.062 g, 0.27 mmol), as prepared in the preceding step, 2-(3-hydroxypropyl)aminopyridine (0.06 g, 0.40 mmol), as prepared in step b of Example 1, and tri-n-butylphosphine (0.11 g, 0.53 mmol) in tetrahydrofuran (6.0 mL). After stirring at ambient temperature overnight (16 h), the reaction was concentrated and the residue was purified by flash chromatography on silica gel (10%-50% ethyl acetate in hexane) to give the title compound as a yellow oil (0.015 g, 15%). 1H-NMR (400 MHz, CDCl3) δ 8.07 (m, 1H), 7.40 (m, 1H), 7.21 (d, J=8.9 Hz, 1H), 7.08 (d, J=2.4 Hz, 1H), 7.04 (d, J=3.1 Hz, 1H), 6.88 (dd, J=8.9, 2.4 Hz, 1H), 6.54 (m, 1H), 6.41 (m, 1H), 4.89 (br s, 1H), 4.45 (dd, J=14.2, 7.3 Hz, 1H), 4.10 (m, 4H), 3.63 (s, 3H), 5.52 (q, J=6.5 Hz, 2H), 2.13 (m, 2H), 1.66 (m, 1H), 1.52 (m, 1H), 1.16 (d, J=7.1 Hz, 3H), 0.93 (m, 3H).

Workup

  1. concentrationthe reaction was concentrated
  2. customthe residue was purified by flash chromatography on silica gel (10%-50% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-e724b7b333af496db07702f573ec598c
Source dataset
uspto-grants-2005_02
Patent number
US06855722B2

Reaction notes

Loading…