Water → 1-[6-[3-Amino-5-(4-morpholinyl)phenyl]-2-pyridinyl]cyclobutanol

HRID 2207353Notes

Reaction equation

[Cl-].[NH4+].[N:3]1([C:9]2[CH:10]=[C:11]([C:18]3[N:23]=[C:22]([C:24]4([OH:28])[CH2:27][CH2:26][CH2:25]4)[CH:21]=[CH:20][CH:19]=3)[CH:12]=[C:13]([N+:15]([O-])=O)[CH:14]=2)[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.O>C(O)C.[Fe]>[NH2:15][C:13]1[CH:12]=[C:11]([C:18]2[N:23]=[C:22]([C:24]3([OH:28])[CH2:27][CH2:26][CH2:25]3)[CH:21]=[CH:20][CH:19]=2)[CH:10]=[C:9]([N:3]2[CH2:8][CH2:7][O:6][CH2:5][CH2:4]2)[CH:14]=1

Participants

Conditions

Temperature: 85 °C

Procedure

Ammonium chloride (22.6 mg, 0.422 mmol) and iron (216 mg, 3.57 mmol) were added to a solution of 1-{6-[3-(morpholin-4-yl)-5-nitrophenyl]pyridin-2-yl}cyclobutanol (250 mg, 0.703 mmol) in ethanol (4.69 mL) and water (2.36 mmol). The reaction mixture was heated to 85° C. for 1 hour, then cooled to room temperature. The reaction was filtered, diluted with water, extracted with ethyl acetate, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (7:3 ethyl acetate:hexanes, then 100% ethyl acetate) to afford 1-{6-[3-amino-5-(morpholin-4-yl)phenyl]pyridin-2-yl}cyclobutanol as an off-white solid. 1H NMR (500 MHz, CDCl3) δ 7.83 (s, 1H), 7.66-7.58 (m, 1H), 7.56 (d, J=7.5, 1H), 7.36-7.23 (m, 2H), 7.01 (s, 1H), 6.90 (s, 1H), 6.34 (s, 1H), 5.81 (s, 1H), 3.90 (m, 4H), 3.23 (m, 4H), 2.64-2.54 (m, 4H), 2.14-2.08 (m, 1H), 1.96-1.92 (m, 1H).

Workup

temperaturecooled to room temperature
filtrationThe reaction was filtered
additiondiluted with water
extractionextracted with ethyl acetate
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe residue was purified by silica gel chromatography (7:3 ethyl acetate

Sources & evidence

ORD record: ord-d7fccdfaae3a4f0bbc2113868e1bd133
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09376418B2

Reaction notes

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