Hydrochloric Acid → HCID 69076836, compound

HRID 225479Notes

Reaction equation

HRID 225479 reaction equation
C([O:9][CH2:10][CH2:11][N:12]1[CH:38]=[C:15]2[CH2:16][N:17]([C:20]3[C:21]4[S:37][CH:36]=[CH:35][C:22]=4[N:23]=[C:24]([C:26]4[CH:31]=[C:30]([F:32])[C:29]([Cl:33])=[CH:28][C:27]=4[F:34])[N:25]=3)[CH2:18][CH2:19][C:14]2=[N:13]1)(=O)C1C=CC=CC=1.[OH-].[Na+].Cl>C1COCC1.CCO>[ClH:33].[Cl:33][C:29]1[C:30]([F:32])=[CH:31][C:26]([C:24]2[N:25]=[C:20]([N:17]3[CH2:18][CH2:19][C:14]4=[N:13][N:12]([CH2:11][CH2:10][OH:9])[CH:38]=[C:15]4[CH2:16]3)[C:21]3[S:37][CH:36]=[CH:35][C:22]=3[N:23]=2)=[C:27]([F:34])[CH:28]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 69075915HCID 69075915, compound

Product 1

HCID 69076836HCID 69076836, compoundYield 218.7%

Reagents, catalysts & solvents 1

HCID 21873804Tetrahydrofuran ethanolSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 1.41 g of 4-chloro-2-(4-chloro-2,5-difluorophenyl)thieno[3,2-d]pyrimidine, 1.28 g of a mixture of 2-(4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-1-yl)ethanol and 2-(4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine-2-yl)ethanol, 3.87 ml of diisopropyl ethylamine and 30 ml of acetonitrile was stirred for 12 hours at 80° C. After 100 ml of water was added to the reaction mixture and extracted with EtOAc, the organic layer was dried over anhydrous magnesium sulfate and the solvent was removed under reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform-MeOH) and 1.19 g of a foam-like substance was obtained. A mixture of the obtained foam-like substances 10 ml of pyridine and 0.62 ml of benzoyl chloride was stirred for one hour at room temperature. After 50 ml of water was added to the reaction mixture and extracted with EtOAc-THF mixed solvents the organic layer was dried over anhydrous magnesium sulfate and the solvent was removed under reduced pressure. The obtained residue was recrystallized from EtOAc and the mother liquid was repeated recrystallization from EtOAc to give 716 mg of 2-{5-[2-(4-chloro-2,5-difluorophenyl)thieno[3,2-d]pyrimidine-4-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine-2-yl}ethyl benzoate was obtained. Further, this recrystallized mother liquid washed with ether-hexane mixed solvent and the washed liquid was concentrated under reduced pressure to give 636 mg of 2-{5-[2-(4-chloro-2,5-difluorophenyl)thieno[3,2-d]pyrimidine-4-yl]-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-1-yl}ethyl benzoate. 716 mg of the obtained 2-{5-[2-(4-chloro-2,5-difluorophenyl)thieno-[3,2-d]pyrimidine-4-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine-2-yl}ethyl benzoate was dissolved in 10 ml of THF-EtOH (2:1) solution and was added to 2.60 ml of 1M NaOH aq. The resultant was stirred for one hour at 60° C. and was left to cool to room temperature. Then, 30 ml of 1M HCl aq was added and washed with ether, the aqueous layer was made alkaline with 100 ml of 1M NaOH aq. After this was extracted with EtOAc, the organic layer was dried over anhydrous magnesium sulfate and the solution was removed under reduced pressure. The obtained residue was dissolved in 20 ml of THF and 10 ml of MeOH, and was added to 3 ml of 4M HCl-dioxane solution, concentrated under reduced pressure and a solid was obtained. This solid was recrystallized from EtOH-EtOAc to give 687 mg of 2-{5-[2-(4-chloro-2,5-difluorophenyl)thieno[3,2-d]pyrimidine-4-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine-2-yl}ethanol hydrochloride. Furthermore, the above-mentioned operation was carried out on the 636 mg of 2-{5-[2-(4-chloro-2,5-difluorophenyl)thieno[3,2-d]pyrimidine-4-yl]-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-1-yl}ethyl benzoate to give 180 mg of 2-{5-[2-(4-chloro-2,5-difluorophenyl)thieno[3,2-d]pyrimidine-4-yl]-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-1-yl}ethanol hydrochloride.

Workup

  1. waitwas left
  2. temperatureto cool to room temperature
  3. washwashed with ether
  4. extractionthis was extracted with EtOAc
  5. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  6. customthe solution was removed under reduced pressure
  7. dissolutionThe obtained residue was dissolved in 20 ml of THF
  8. addition10 ml of MeOH, and was added to 3 ml of 4M HCl-dioxane solution
  9. concentrationconcentrated under reduced pressure
  10. customa solid was obtained
  11. customThis solid was recrystallized from EtOH-EtOAc

Sources & evidence

ORD record
ord-a3c70cc31a144e0f8da174985daf47c5
Source dataset
uspto-grants-2009_07
Patent number
US07557112B2

Reaction notes

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