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

HRID 1775578ノート

反応式

HRID 1775578 の反応式
[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

参加物

6

反応物 5

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

生成物 1

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

反応条件

温度
-10 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-1714bd83bef247aab2911a0cc1baedbf
出典データセット
uspto-grants-2016_02
特許番号
US09260381B2

反応ノート

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