Water → HCID 178515334, compound

HRID 1775581Notes

Reaction equation

[N:1]([O-])=O.[Na+].[F:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[C:16]([C:17]#[C:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[C:15]([NH2:25])[N:14]([CH2:26][CH2:27][N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[N:13]=2)=[CH:8][CH:7]=1.[OH2:34].C(Cl)Cl>Cl.FC(F)(F)C(O)=O>[F:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[C:16]3[C:17]([OH:34])=[C:18]([C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)[N:1]=[N:25][C:15]=3[N:14]([CH2:26][CH2:27][N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[N:13]=2)=[CH:8][CH:7]=1

Participants

Conditions

Temperature: -10 °C

Procedure

To a cooled (cooling bath −10° C.) stirred suspension of sodium nitrite (82 mg, 1.2 mmol) in conc. HCl (2.6 mL) was added a solution of 3-(4-fluorophenyl)-1-(2-morpholinoethyl)-4-(phenylethynyl)-1H-pyrazol-5-amine (129 mg, 0.33 mmol) in trifluoroacetic acid (0.5 ml) and the reaction mixture was allowed to warm to ambient temperature over 2 h. Water and CH2Cl2 were added. The aqueous phase was extracted with CH2Cl2 (×3) and the organic phases combined, dried over MgSO4, filtered and evaporated. The crude material was purified by preparative HPLC to give 3-(4-fluorophenyl)-1-(2-morpholinoethyl)-5-phenyl-1H-pyrazolo[3,4-c]pyridazin-4-ol as a solid (27.8 mg) which was used as such in the subsequent step.

Workup

temperatureTo a cooled
temperatureto warm to ambient temperature over 2 h
extractionThe aqueous phase was extracted with CH2Cl2 (×3)
dry with materialdried over MgSO4
filtrationfiltered
customevaporated
customThe crude material was purified by preparative HPLC

Sources & evidence

ORD record: ord-d9cf4926103241fcaa27abac54c27afd
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09260381B2

Reaction notes

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