Hydrochloric Acid → HCID 70982950, compound

HRID 1479197Notes

Reaction equation

HRID 1479197 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([C:20](=[O:42])[NH:21][C:22]3[C:30]4[C:25](=[CH:26][C:27]([O:31][CH2:32][CH2:33][O:34][CH2:35][C:36]5[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=5)=[CH:28][CH:29]=4)[NH:24][N:23]=3)=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.Cl>O1CCOCC1.CO>[CH2:35]([O:34][CH2:33][CH2:32][O:31][C:27]1[CH:26]=[C:25]2[C:30]([C:22]([NH:21][C:20](=[O:42])[C:17]3[CH:18]=[CH:19][C:14]([N:11]4[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]4)=[CH:15][CH:16]=3)=[N:23][NH:24]2)=[CH:29][CH:28]=1)[C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 70983385HCID 70983385, compound

Product 1

HCID 70982950HCID 70982950, compoundYield 75.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent2×

Procedure

A solution of 4-{4-[6-(2-benzyloxy-ethoxy)-1H-indazol-3-ylcarbamoyl]-phenyl}-piperazine-1-carboxylic acid tert-butyl ester (180 mg, 0.31 mmol) in 1,4-dioxane (10 ml) and MeOH (5 ml) was treated with 4M hydrochloric acid in 1,4-dioxane (6 ml, 24 mmol). After stirring for 2 h at r.t. the reaction mixture was evaporated to dryness, diluted with water (50 ml) and brought to basic pH by addition of a saturated solution of NaHCO3. The precipitated solid was filtered, washed with water, dried and purified by chromatography (Biotage SP1 Flash Purification system) on a silica gel cartridge (Biotage SNAP 25 g) using DCM as eluant A and DCM/7N NH3 in MeOH 10:1 as eluant B. Elution with a gradient from A/B 100:0 to 0:100 over 15 CV, followed by an isocratic elution with eluant B (5 CV), gave a yellow solid that was triturated with diethyl ether (15 ml) affording 111 mg (yield: 75%) of the title compound as a white solid.

Workup

  1. customwas evaporated to dryness
  2. additiondiluted with water (50 ml)
  3. additionbrought to basic pH by addition of a saturated solution of NaHCO3
  4. filtrationThe precipitated solid was filtered
  5. washwashed with water
  6. customdried
  7. custompurified by chromatography (Biotage SP1 Flash Purification system) on a silica gel cartridge (Biotage SNAP 25 g)
  8. washElution with a gradient from A/B 100:0 to 0:100 over 15 CV
  9. washfollowed by an isocratic elution with eluant B (5 CV)
  10. customgave a yellow solid
  11. customthat was triturated with diethyl ether (15 ml)

Sources & evidence

ORD record
ord-0d55906b984844b8a55f983664de4d6f
Source dataset
uspto-grants-2016_08
Patent number
US09408850B2

Reaction notes

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