Hydrochloric Acid → HCID 44603147, compound

HRID 79065Notes

Reaction equation

HRID 79065 reaction equation
C([O:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[C:11]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([S:26][CH3:27])=[CH:22][C:21]=2[F:28])=[C:12]2[C:16](=[CH:17][CH:18]=1)[NH:15][N:14]=[CH:13]2)=[O:9])=C.Cl>CO>[OH:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[C:11]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([S:26][CH3:27])=[CH:22][C:21]=2[F:28])=[C:12]2[C:16](=[CH:17][CH:18]=1)[NH:15][N:14]=[CH:13]2)=[O:9]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 866562484-(2-fluoro-4-methylsulfanyl-phenylamino)-1H-indazole-5-carboxylic acid (2-vinyloxy-ethoxy)-amide

Product 1

HCID 44603147HCID 44603147, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 4-(2-fluoro-4-methylsulfanyl-phenylamino)-1H-indazole-5-carboxylic acid (2-vinyloxy-ethoxy)-amide (45 mg, 0.112 mmol) in methanol (5 mL) was treated with hydrochloric acid (1M, 0.225 mL, 0.22 mmol) and the reaction mixture stirred at room temperature for 2 hours. The reaction mixture was then concentrated in vacuo and the residue dissolved in methanol and to this solution was added water causing a precipitate to form which was filtered off. The filtrate was extracted twice with ethyl acetate, the combined extracts dried (Na2SO4), filtered and concentrated in vacuo. The crude product was combined with the earlier solid precipitate and subjected to flash chromatography (Si—PPC, gradient 0 to 10% methanol in DCM) to give a solid. The solid was triturated in diethyl ether to give a pale tan solid (23 mg, 55%). LCMS (Method A) RT 7.79 [M+H]+ 377. 1H NMR (MeOD, 400 MHz): 7.52-7.44 (1 H, m), 7.21-7.09 (3 H, m), 7.06 (1 H, dd, J=8.41, 2.08 Hz), 6.93 (1 H, d, J=8.88 Hz), 4.54 (1 H, s), 4.02-3.98 (2 H, m), 3.75 (2 H, dd, J=5.28, 4.05 Hz), 2.48 (3 H, s).

Workup

  1. concentrationThe reaction mixture was then concentrated in vacuo
  2. dissolutionthe residue dissolved in methanol and to this solution
  3. additionwas added water causing a precipitate
  4. customto form which
  5. filtrationwas filtered off
  6. extractionThe filtrate was extracted twice with ethyl acetate
  7. dry with materialthe combined extracts dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give a solid
  11. customThe solid was triturated in diethyl ether

Sources & evidence

ORD record
ord-60a59dc9684a41c58934cd3cd09d3a25
Source dataset
uspto-grants-2014_09
Patent number
US08841462B2

Reaction notes

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