(Pyrrolidin-3-yl)methanol → 5-(1H-pyrazol-1-yl)-2-(6-(pyrrolidin-3-ylmethoxy)pyridazin-3-yl)phenol

HRID 1027191Notes

Reaction equation

CC(C)([O-])C.[K+].[NH:7]1[CH2:11][CH2:10][CH:9]([CH2:12][OH:13])[CH2:8]1.Cl[C:15]1[N:20]=[N:19][C:18]([C:21]2[CH:26]=[CH:25][C:24]([N:27]3[CH:31]=[CH:30][CH:29]=[N:28]3)=[CH:23][C:22]=2[OH:32])=[CH:17][CH:16]=1>C1COCC1>[N:27]1([C:24]2[CH:25]=[CH:26][C:21]([C:18]3[N:19]=[N:20][C:15]([O:13][CH2:12][CH:9]4[CH2:10][CH2:11][NH:7][CH2:8]4)=[CH:16][CH:17]=3)=[C:22]([OH:32])[CH:23]=2)[CH:31]=[CH:30][CH:29]=[N:28]1

Participants

Conditions

Temperature: 50 °C

Procedure

Potassium tert-butoxide (1.0 M in THF, 0.7 mL, 0.7 mmol) was added to pyrrolidin-3-ylmethanol (0.06 g, 0.64 mmol) in THF (1.4 mL) and the mixture was stirred for 10 min at 50° C. 2-(6-Chloropyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol Intermediate 2-2 (0.05 g, 0.18 mmol) was added to the reaction at 0° C. and the mixture was stirred for 1 h at RT. Solvent was evaporated under reduced pressure. The crude material was purified via reverse phase preparative HPLC (5 to 95% acetonitrile in water, 5 mM NH4OH as modifier). Enantiomer 1 and Enantiomer 2 were isolated via preparative SFC. Two solids (11 mg (17%), and 12 mg (20%) were afforded.

Workup

stirringthe mixture was stirred for 1 h at RT
customSolvent was evaporated under reduced pressure
customThe crude material was purified via reverse phase preparative HPLC (5 to 95% acetonitrile in water, 5 mM NH4OH as modifier)
customEnantiomer 1 and Enantiomer 2 were isolated via preparative SFC
customTwo solids (11 mg (17%), and 12 mg (20%) were afforded

Sources & evidence

ORD record: ord-e6b232cb170244a1b640b3627c8b172d
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08729263B2

Reaction notes

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