2-Methoxyethanol → HCID 66898014, compound

HRID 1188961Notes

Reaction equation

HRID 1188961 reaction equation
[F:1][C:2]1[C:10]([OH:11])=[C:9]2[C:5]([CH:6]=[C:7]([C:12]([NH2:14])=[O:13])[NH:8]2)=[CH:4][C:3]=1[O:15][C:16]1[CH:17]=[N:18][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:20][CH:21]=1.[CH3:26][O:27][CH2:28][CH2:29]O.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>O1CCCC1>[F:1][C:2]1[C:10]([O:11][CH2:29][CH2:28][O:27][CH3:26])=[C:9]2[C:5]([CH:6]=[C:7]([C:12]([NH2:14])=[O:13])[NH:8]2)=[CH:4][C:3]=1[O:15][C:16]1[CH:17]=[N:18][C:19]([S:22]([CH3:25])(=[O:23])=[O:24])=[CH:20][CH:21]=1

Participants

6

Reactant 4

HCID 80192-Methoxyethanol3×HCID 13831Tributylphosphine3×HCID 730421,1'-(Azodicarbonyl)dipiperidine3×HCID 58236955HCID 58236955, compound

Product 1

HCID 66898014HCID 66898014, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 6-fluoro-7-hydroxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indole-2-carboxamide (0.98 g), 2-methoxyethanol (0.43 mL), tributylphosphine (1.24 mL) and 1,1′-(azodicarbonyl)dipiperidine (1.35 g) in tetrahydrofuran (130 ml) was stirred at 50° C. for 6 h under argon atmosphere. To the mixture were added 2-methoxyethanol (0.43 mL), tributylphosphine (1.24 mL) and 1,1′-(azodicarbonyl)dipiperidine (1.35 g) and the mixture was stirred at 50° C. for 15 h under argon atmosphere. Furthermore, 2-methoxyethanol (0.43 mL), tributylphosphine (1.24 mL) and 1,1′-(azodicarbonyl)dipiperidine (1.35 g) were added to the mixture. After stirred at 50° C. for 18 h under argon atmosphere, the mixture was concentrated in vacuo. The resulting insoluble materials were filtered off and the filtrate was concentrated in vacuo. The residue was purified by basic silica gel chromatography (ethyl acetate:hexane=30:70 to 100:0, volume ratio) to give the title compound (0.61 g, 54%) as a pale pink amorphous solid. MS 424 (MH+).

Workup

  1. stirringthe mixture was stirred at 50° C. for 15 h under argon atmosphere
  2. stirringAfter stirred at 50° C. for 18 h under argon atmosphere
  3. concentrationthe mixture was concentrated in vacuo
  4. filtrationThe resulting insoluble materials were filtered off
  5. concentrationthe filtrate was concentrated in vacuo
  6. customThe residue was purified by basic silica gel chromatography (ethyl acetate:hexane=30:70 to 100:0, volume ratio)

Sources & evidence

ORD record
ord-c6c8b6f3b6f84d8db404b2218f4a7abb
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Reaction notes

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