Water → HCID 57891924, compound

HRID 1821030Notes

Reaction equation

[C:1]([C:3]1[CH:4]=[C:5]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:19]=[C:20]4[C:24](=[CH:25][C:26]=3[CH3:27])[CH:23]([CH2:28][C:29]([O:31]C)=[O:30])[CH2:22][CH2:21]4)[N:14]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:12])[CH3:11])#[N:2].O>C1COCC1>[C:1]([C:3]1[CH:4]=[C:5]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:19]=[C:20]4[C:24](=[CH:25][C:26]=3[CH3:27])[CH:23]([CH2:28][C:29]([OH:31])=[O:30])[CH2:22][CH2:21]4)[N:14]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:12])[CH3:11])#[N:2]

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of methyl (5-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-6-methyl indan-1-yl)acetate (23.0 mg, 0.053 mmol, from Step H) in THF (2 mL) and H2O (0.7 mL) lithium hydroxide monohydrate (4.0 mg, 0.107 mmol) was added. The reaction mixture was heated to 50° C. for 3 hr, cooled to ambient temperature and partitioned between EtOAc and 5% citric acid. The organic layer was washed with H2O, brine, dried over MgSO4, filtered and concentrated in vacuo. Purification of the residue by flash chromatography (2% CH3OH/CH2Cl2/0.2% HCO2H) on SiO2 afforded 28.0 mg of the title compound as a white film: 1H NMR (500 MHz, DMSO-d6) δ 1.34 (d, 6H, J=5.9 Hz), 1.60-1.74 (m, 1H), 2.25-2.39 (m, 2H), 2.55 (s, 3H), 2.64-2.92 (m, 3H), 3.42-3.47 (m, 1H), 4.85-5.05 (m, 1H), 7.32 (s, 1H), 7.56 (d, 1H, J=9.4 Hz), 7.86 (s, 1H), 8.38 (d, 1H, J=9.6 Hz), 8.51 (s, 1H); HPLC A: rt=3.84 min, m/z=418.5 (M+H)+.

Workup

temperaturecooled to ambient temperature
custompartitioned between EtOAc and 5% citric acid
washThe organic layer was washed with H2O, brine
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated in vacuo
customPurification of the residue by flash chromatography (2% CH3OH/CH2Cl2/0.2% HCO2H) on SiO2

Sources & evidence

ORD record: ord-0c6e489b77b342d1a147faf82c59889c
Source dataset: uspto-grants-2009_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07605171B2

Reaction notes

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