1,3-Dimethoxy-2-propanol → Methyl 7-[2-methoxy-1-(methoxymethyl)ethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indole-2-carboxylate

HRID 1188912

Reaction equation

HRID 1188912 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([O:15][C:16]2[CH:17]=[N:18][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:20][CH:21]=2)[CH:5]=[C:6]2[C:10]=1[NH:9][C:8]([C:11]([O:13][CH3:14])=[O:12])=[CH:7]2.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.[CH3:57][O:58][CH2:59][CH:60](O)[CH2:61][O:62][CH3:63]>O1CCCC1>[CH3:57][O:58][CH2:59][CH:60]([CH2:61][O:62][CH3:63])[O:1][C:2]1[CH:3]=[C:4]([O:15][C:16]2[CH:17]=[N:18][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:20][CH:21]=2)[CH:5]=[C:6]2[C:10]=1[NH:9][C:8]([C:11]([O:13][CH3:14])=[O:12])=[CH:7]2

Participants

6

Reactant 4

HCID 121901,3-Dimethoxy-2-propanol3×HCID 13831Tributylphosphine3×HCID 730421,1'-(Azodicarbonyl)dipiperidine3×HCID 66897290Methyl 7-hydroxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indole-2-carboxylate

Product 1

HCID 66897495Methyl 7-[2-methoxy-1-(methoxymethyl)ethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indole-2-carboxylateYield 116.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of methyl 7-hydroxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indole-2-carboxylate (1.2 g), tributylphosphine (1.6 mL), 1,1′-(azodicarbonyl)dipiperidine (1.7 g), 1,3-dimethoxypropan-2-ol (0.8 g) and tetrahydrofuran (20 mL) was stirred at 50° C. for 13 h. Tributylphosphine (0.82 mL), 1,1′-(azodicarbonyl)dipiperidine (0.83 g) and 1,3-dimethoxypropan-2-ol (0.4 g) were added to the mixture again and the mixture was stirred at 70° C. for 5 h. Furthermore, tributylphosphine (1.64 mL), 1,1′-(azodicarbonyl)dipiperidine (1.66 g) and 1,3-dimethoxypropan-2-ol (0.8 g) were added to the mixture. After stirring at 70° C. for 3 h, the mixture was cooled to 0° C., and insoluble materials were removed by filtration. The filtrate was concentrated and the residue was purified basic silica gel column chromatography (ethyl acetate/hexane=20/80 to 85/15, volume ratio) to give the title compound (1.79 g, 84%) as an orange oil, MS 463 (MH−).

Workup

  1. stirringthe mixture was stirred at 70° C. for 5 h
  2. stirringAfter stirring at 70° C. for 3 h
  3. temperaturethe mixture was cooled to 0° C.
  4. custominsoluble materials were removed by filtration
  5. concentrationThe filtrate was concentrated
  6. customthe residue was purified basic silica gel column chromatography (ethyl acetate/hexane=20/80 to 85/15, volume ratio)

Sources & evidence

ORD record
ord-a08066e159044363ac0c078d373e5c44
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Linked notes

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