p-Toluenesulfonic acid monohydrate → HCID 86732438, compound

HRID 1776409Notes

Reaction equation

HRID 1776409 reaction equation
C([O:3][C:4]([C:6]1[CH:36]=[C:35]([F:37])[C:9]([CH2:10][N:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]([C:20]3[N:25]=[C:24]([NH:26][C:27]4[CH:32]=[CH:31][N:30]=[CH:29][CH:28]=4)[C:23]([O:33][CH3:34])=[CH:22][N:21]=3)=[N:12]2)=[C:8]([F:38])[CH:7]=1)=[CH2:5])C.O.CC1C=CC(S(O)(=O)=O)=CC=1>C(O)C.O>[F:37][C:35]1[CH:36]=[C:6]([C:4](=[O:3])[CH3:5])[CH:7]=[C:8]([F:38])[C:9]=1[CH2:10][N:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]([C:20]2[N:25]=[C:24]([NH:26][C:27]3[CH:32]=[CH:31][N:30]=[CH:29][CH:28]=3)[C:23]([O:33][CH3:34])=[CH:22][N:21]=2)=[N:12]1

Participants

5

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 86732437HCID 86732437, compound

Product 1

HCID 86732438HCID 86732438, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

119 mg of 2-{1-[4-(1-ethoxyethenyl)-2,6-difluorobenzyl]-1H-indazol-3-yl}-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amine (0.231 mmol, 1 eq.) and 66 mg of 4-methylbenzenesulfonic acid hydrate (1:1) (0.347 mmol, 1.5 eq.) were dissolved in 2.4 ml of ethanol and 0.6 ml of water. The mixture was stirred for one hour at 80° C. bath temperature. The reaction mixture was concentrated in vacuo. The residue was partitioned between ethyl acetate and saturated sodium hydrogen carbonate solution. The phases were separated and the aqueous layer was extracted twice with ethyl acetate. The combined organic layers were dried over magnesium sulfate and concentrated in vacuo. The residue was purified by flash chromatography and preparative HPLC purification to yield 26 mg (0.05 mmol, 22.7%) of the analytically pure target compound.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customThe residue was partitioned between ethyl acetate and saturated sodium hydrogen carbonate solution
  3. customThe phases were separated
  4. extractionthe aqueous layer was extracted twice with ethyl acetate
  5. dry with materialThe combined organic layers were dried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography and preparative HPLC purification
  8. customto yield 26 mg (0.05 mmol, 22.7%) of the analytically pure target compound

Sources & evidence

ORD record
ord-08955639d2294a41b57c6a4401ccce4b
Source dataset
uspto-grants-2016_02
Patent number
US09265763B2

Reaction notes

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