HCID 86732422, compound → HCID 86732423, compound

HRID 1776395Notes

Reaction equation

HRID 1776395 reaction equation
[CH3:1][O:2][C:3]1[C:4]([N:25]([C:32]([O:34][CH2:35][CH:36]=[CH2:37])=[O:33])[C:26]2[CH:31]=[CH:30][N:29]=[CH:28][CH:27]=2)=[N:5][C:6]([C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11](C(OC(C)(C)C)=O)[N:10]=2)=[N:7][CH:8]=1.[H][H]>O1CCOCC1>[CH2:35]([O:34][C:32](=[O:33])[N:25]([C:4]1[C:3]([O:2][CH3:1])=[CH:8][N:7]=[C:6]([C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[NH:11][N:10]=2)[N:5]=1)[C:26]1[CH:27]=[CH:28][N:29]=[CH:30][CH:31]=1)[CH:36]=[CH2:37]

Participants

4

Reactant 2

HCID 86732422HCID 86732422, compoundHCID 178418361HCID 178418361, compound2×

Product 1

HCID 86732423HCID 86732423, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent3×

Procedure

1.22 g of tert-butyl 3-(5-methoxy-4-{[(prop-2-en-1-yloxy)carbonyl](pyridin-4-yl)amino}pyrimidin-2-yl)-1H-indazole-1-carboxylate (1-9-1, 2.43 mmol, 1 eq.) was suspended in 1,4-dioxane. 2.43 ml of hydrogen acid 4M in 1,4-dioxane (9.711 mmol, 4 eq.) were added dropwise. The reaction mixture was stirred for 24 hours at room temperature. 2.43 ml of hydrogen acid 4M in 1,4-dioxane (9.711 mmol, 4 eq.) were added dropwise again and stirred for further two hours. The reaction mixture was concentrated under vacuo. The residue was extracted with saturated aq. sodium hydrogen carbonate-solution and ethyl acetate. The aqueous layer was reextracted twice by ethyl acetate. The combined organic layers were dried over a silicone filter and concentrated under vacuo. Purification by flash chromatography (ethyl acetate/methanol 0-25%) provided 877 mg (1.96 mmol, 80.8%) of the analytically pure target compound.

Workup

  1. stirringstirred for further two hours
  2. concentrationThe reaction mixture was concentrated under vacuo
  3. extractionThe residue was extracted with saturated aq. sodium hydrogen carbonate-solution and ethyl acetate
  4. dry with materialThe combined organic layers were dried over a silicone
  5. filtrationfilter
  6. concentrationconcentrated under vacuo
  7. customPurification by flash chromatography (ethyl acetate/methanol 0-25%)
  8. customprovided 877 mg (1.96 mmol, 80.8%) of the analytically pure target compound

Sources & evidence

ORD record
ord-f021f474980a48e4ab5bf32d59b4579b
Source dataset
uspto-grants-2016_02
Patent number
US09265763B2

Reaction notes

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