Hydrochloric Acid → HCID 59272915, compound

HRID 1510600Notes

Reaction equation

HRID 1510600 reaction equation
[F:1][C:2]([F:43])([CH3:42])[C:3]([NH:5][C@@H:6]([CH3:41])[C@@H:7]([C:31]1[CH:40]=[CH:39][C:34]2[O:35][CH2:36][CH2:37][O:38][C:33]=2[CH:32]=1)[O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([C:18]1[CH:19]=[C:20]([CH:28]=[CH:29][CH:30]=1)[C:21]([O:23]CC(C)C)=[O:22])[N:13]=[CH:12]2)=[O:4].[OH-].[Na+].Cl>C1COCC1.C(#N)C>[F:43][C:2]([F:1])([CH3:42])[C:3]([NH:5][C@@H:6]([CH3:41])[C@@H:7]([C:31]1[CH:40]=[CH:39][C:34]2[O:35][CH2:36][CH2:37][O:38][C:33]=2[CH:32]=1)[O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([C:18]1[CH:19]=[C:20]([CH:28]=[CH:29][CH:30]=1)[C:21]([OH:23])=[O:22])[N:13]=[CH:12]2)=[O:4]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium Hydroxide2×HCID 59272930HCID 59272930, compound

Product 1

HCID 59272915HCID 59272915, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of isobutyl 3-(5-((1R,2S)-2-(2,2-difluoropropanamido)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)propoxy)-1H-indazol-1-yl)benzoate (I4a) (350 mg, 0.59 mmol) in THF (5 mL) and acetonitrile (2 mL) was treated with 0.25 M NaOH (4.72 mL, 1.18 mmol). The mixture was stirred at ambient temperature for 23 hours, additional 1M NaOH (0.590 mL, 0.59 mmol) was added and the mixture was stirred at +45° C. for 2 hours. The reaction mixture was allowed to cool down and acidified to pH 2.5-3 by adding 1 N HCl. Addition of THF and MeCN until solution followed by purification by HPLC, using an Kromasil 100-10-C18, 50×250 mm column, an 30 min gradient from 50% to 90% MeCN in water+0.1% TFA in solvents with flow=40 mL/min and UV=254 nm to collect fractions. Fractions containing the product was combined and freezedried. The material was redissolved in tBuOMe, addition of Heptane gave precipitation, the formed slurry was evaporated to afford the subtitle compound as a colourless solid. Yield 315 mg (99%)

Workup

  1. stirringthe mixture was stirred at +45° C. for 2 hours
  2. temperatureto cool down
  3. customfollowed by purification by HPLC
  4. customan 30 min gradient from 50% to 90% MeCN in water+0.1% TFA in solvents with flow=40 mL/min and UV=254 nm to collect fractions
  5. additionFractions containing the product
  6. customfreezedried
  7. dissolutionThe material was redissolved in tBuOMe
  8. additionaddition of Heptane
  9. customgave
  10. customprecipitation
  11. customthe formed slurry was evaporated

Sources & evidence

ORD record
ord-f6d721894ba44309ad07041b1bca02d5
Source dataset
uspto-grants-2012_07
Patent number
US08211930B2

Reaction notes

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