Triphenylphosphine → methyl 2-(5-{3-[(5-cyano-2-pyridinyl)oxy]propoxy}-1H-indol-1-yl)propanoate

HRID 734428Notes

Reaction equation

HRID 734428 reaction equation
[OH:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:13]=[CH:12][C:9]([C:10]#[N:11])=[CH:8][N:7]=1.[CH3:14][O:15][C:16](=[O:29])[CH:17]([N:19]1[C:27]2[C:22](=[CH:23][C:24](O)=[CH:25][CH:26]=2)[CH:21]=[CH:20]1)[CH3:18].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C(Cl)Cl>[C:10]([C:9]1[CH:12]=[CH:13][C:6]([O:5][CH2:4][CH2:3][CH2:2][O:1][C:24]2[CH:23]=[C:22]3[C:27](=[CH:26][CH:25]=2)[N:19]([CH:17]([CH3:18])[C:16]([O:15][CH3:14])=[O:29])[CH:20]=[CH:21]3)=[N:7][CH:8]=1)#[N:11]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 431521396-(3-Hydroxypropoxy)nicotinonitrileHCID 57845447methyl 2-(5-hydroxy-1H-indol-1-yl)propanoate

Product 1

HCID 57845394methyl 2-(5-{3-[(5-cyano-2-pyridinyl)oxy]propoxy}-1H-indol-1-yl)propanoateYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 6-(3-hydroxypropoxy)nicotinonitrile (Example 66, 0.55 g, 3.09 mmol) and methyl 2-(5-hydroxy-1H-indol-1-yl)propanoate (Example 7, 0.34 g, 1.55 mmol) in CH2Cl2 (7.73 mL) were added triphenylphosphine (0.61 g, 2.32 mmol) and 1,1′-(azodicarbonyl)-dipiperidine (0.59 g, 2.32 mmol). The yellow reaction mixture was stirred at rt for 18 h and then concentrated under reduced pressure. The crude residue was purified by silica gel column chromatography (eluting with 67% hexanes/EtOAc) to give the title compound (0.5 g, 85%). 1H NMR (400 MHz, CD2Cl2) δ 8.49 (dd, 1H), 7.79 (dd, 1H), 7.25-7.09 (m, 3H), 6.85-6.83 (m, 2H), 6.47 (d, 1H), 5.11 (qt, 1H), 4.60 (t, 2H), 4.17 (t, 2H), 3.71 (s, 3H), 2.35-2.25 (m, 2H), 1.82 (d, 3H).

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe crude residue was purified by silica gel column chromatography (eluting with 67% hexanes/EtOAc)

Sources & evidence

ORD record
ord-3ecbe98e917b440eb9b49065bdccd9c7
Source dataset
uspto-grants-2009_09
Patent number
US07592361B2

Reaction notes

Loading…