Sodium → N-(2-Hydroxymethylthiazolo[5,4-b]pyrid-6-yl)-5-fluoro-1-[(3-fluorophenyl)methyl]-1H-indole-2-carboxamide

HRID 2069526Notes

Reaction equation

HRID 2069526 reaction equation
[Na].CC(C)(C)C([O:6][CH2:7][C:8]1[S:9][C:10]2[C:15]([N:16]=1)=[CH:14][C:13]([NH:17][C:18]([C:20]1[N:21]([CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[CH:32]=3)[C:22]3[C:27]([CH:28]=1)=[CH:26][C:25]([F:29])=[CH:24][CH:23]=3)=[O:19])=[CH:12][N:11]=2)=O>CO>[OH:6][CH2:7][C:8]1[S:9][C:10]2[C:15]([N:16]=1)=[CH:14][C:13]([NH:17][C:18]([C:20]1[N:21]([CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[CH:32]=3)[C:22]3[C:27]([CH:28]=1)=[CH:26][C:25]([F:29])=[CH:24][CH:23]=3)=[O:19])=[CH:12][N:11]=2

Participants

4

Reactant 2

HCID 5360545SodiumHCID 66888934HCID 66888934, compound2×

Product 1

HCID 44181666N-(2-Hydroxymethylthiazolo[5,4-b]pyrid-6-yl)-5-fluoro-1-[(3-fluorophenyl)methyl]-1H-indole-2-carboxamideYield 55.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
20 °C

Procedure

50 mg (2.03 mmol) of sodium are added to 8 mL of methanol with stirring at 20° C. After 15 minutes, a solution of 0.15 g (0.28 mmol) of [6-[[[5-fluoro-1-[(3-fluorophenyl)methyl]-1H-indol-2-yl]carbonyl]amino]thiazolo[5,4-b]pyrid-2-yl]methyl 2,2-dimethylpropanoate (Compound 13), prepared in step 4.3, in 16 mL of methanol is added. Stirring is continued for 15 minutes at 20° C., and the reaction mixture is then concentrated under reduced pressure and taken up in 200 mL of molar ammonium chloride solution. The aqueous phase is extracted three times with 50 mL of ethyl acetate. The organic phases are combined, washed with 50 mL of saturated sodium chloride solution and then dried over sodium sulfate and concentrated under reduced pressure. The product thus obtained is purified on a column of silica, eluting with a mixture of dichloromethane and methanol. 70 mg of the expected product are thus isolated.

Workup

  1. additionis added
  2. stirringStirring
  3. waitis continued for 15 minutes at 20° C.
  4. concentrationthe reaction mixture is then concentrated under reduced pressure
  5. extractionThe aqueous phase is extracted three times with 50 mL of ethyl acetate
  6. washwashed with 50 mL of saturated sodium chloride solution
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe product thus obtained
  10. customis purified on a column of silica
  11. washeluting with a mixture of dichloromethane and methanol

Sources & evidence

ORD record
ord-c397f6602dac48dcb40a7624ce67402b
Source dataset
uspto-grants-2012_10
Patent number
US08299114B2

Reaction notes

Loading…