Hydrochloric Acid → 2-(4-chloro-3-(4-fluorophenyl)-5-phenyl-1H-pyrazolo[3,4-c]pyridazin-1-yl)ethanol

HRID 1775578Notes

Reaction equation

HRID 1775578 reaction equation
[N:1]([O-])=O.[Na+].[NH2:5][C:6]1[N:10]([CH2:11][CH2:12]O)[N:9]=[C:8]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[C:7]=1[C:21]#[C:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[OH2:29].C(Cl)Cl.[ClH:33]>>[Cl:33][C:21]1[C:22]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[N:1][N:5]=[C:6]2[N:10]([CH2:11][CH2:12][OH:29])[N:9]=[C:8]([C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=3)[C:7]=12

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 962WaterHCID 6344DichloromethaneHCID 23668193Sodium NitriteHCID 709836322-(5-amino-3-(4-fluorophenyl)-4-(phenylethynyl)-1H-pyrazol-1-yl)ethanol

Product 1

HCID 665761762-(4-chloro-3-(4-fluorophenyl)-5-phenyl-1H-pyrazolo[3,4-c]pyridazin-1-yl)ethanol

Conditions

Temperature
-10 °C

Procedure

To a cooled (cooling bath −10° C.) stirred suspension of sodium nitrite (120 mg, 1.7 mmol) in conc. HCl (3.6 mL) was added 2-(5-amino-3-(4-fluorophenyl)-4-(phenylethynyl)-1H-pyrazol-1-yl)ethanol (183 mg, 0.57 mmol) and the reaction mixture was allowed to warm to ambient temperature over 90 min. Water and CH2Cl2 were added to the reaction mixture. The aqueous phase was extracted with CH2Cl2 (×4) and the organic phases combined, dried over MgSO4, filtered and evaporated the crude material was purified using chromatography (silica gel, gradient 20 to 100% ethyl acetate/isohexane) followed by preparative HPLC yielding Compound 77 as a white solid (6.5 mg).

Workup

  1. temperatureTo a cooled
  2. temperatureto warm to ambient temperature over 90 min
  3. extractionThe aqueous phase was extracted with CH2Cl2 (×4)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated the crude material
  7. customwas purified

Sources & evidence

ORD record
ord-1714bd83bef247aab2911a0cc1baedbf
Source dataset
uspto-grants-2016_02
Patent number
US09260381B2

Reaction notes

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