Isopropanol → HCID 86646463, compound

HRID 1685791Notes

Reaction equation

HRID 1685791 reaction equation
[CH2:1]([N:3]([CH2:6][C:7]1[S:11][C:10]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:22]=[C:21]([CH3:23])[C:20]([OH:24])=[C:19]([CH2:25][CH3:26])[CH:18]=3)[N:13]=2)=[CH:9][C:8]=1[CH3:27])[CH2:4][CH3:5])[CH3:2].[CH:28]([OH:31])([CH3:30])[CH3:29]>[OH-].[Na+].C([C@@H]1OC1)Cl.CC(=O)OCC>[CH2:1]([N:3]([CH2:4][CH3:5])[CH2:6][C:7]1[S:11][C:10]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:22]=[C:21]([CH3:23])[C:20]([O:24][CH2:29][C@@H:28]4[CH2:30][O:31]4)=[C:19]([CH2:25][CH3:26])[CH:18]=3)[N:13]=2)=[CH:9][C:8]=1[CH3:27])[CH3:2]

Participants

6

Reactant 2

HCID 3776IsopropanolHCID 1363773324-[5-(5-Diethylaminomethyl-4-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenol

Product 1

HCID 86646463HCID 86646463, compound

Reagents, catalysts & solvents 3

HCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolventHCID 2734062(-)-EpichlorohydrinSolvent

Procedure

To a solution of 4-[5-(5-diethylaminomethyl-4-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenol (1.49 g, 3.87 mmol) in isopropanol (70 mL) and 3 N aq. NaOH (19 mL), (R)-epichlorohydrine is added. The mixture is stirred at rt for 41 h. The mixture is diluted with EA and washed with 1 M aq. NaOH. The washing is extracted back with EA. The organic extracts are combined, dried over MgSO4, filtered and concentrated. The crude product is purified by prep. HPLC (XBridge C18, 50×50 mm, 10 μm, eluting with a gradient of acetonitrile in water containing 0.5% of concentrated aq. ammonia) to give diethyl-{5-[3-((S)-3-ethyl-5-methyl-4-oxiranylmethoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-3-methyl-thiophen-2-ylmethyl}-amine (990 mg) as a pale yellow resin; LC-MS: tR=0.65 min; [M+1]+=442.09. b) A solution of diethyl-{5-[3-((S)-3-ethyl-5-methyl-4-oxiranylmethoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-3-methyl-thiophen-2-ylmethyl}-amine (450 mg, 1.02 mmol) in 7 N NH3 in methanol is stirred in a sealed vessel at 65° C. for 16 h. The solvent is evaporated and the crude product is purified by prep. HPLC. The product containing fractions are filtered over Amberlyst A21. The filtrate is concentrated and dried to give the title compound (381 mg) as a yellow resin; LC-MS: tR=0.44 min; [M+1]+=459.10; 1H NMR (D6-DMSO): δ1.03 (t, J=7.0 Hz, 6H), 1.23 (t, J=7.5 Hz, 3H), 2.22 (s, 3H), 2.35 (s, 3H), 2.58 (q, J=7.0 Hz, 4H), 2.73 (q, J=7.5 Hz, 2H), 2.88 (dd, J=12.8, 9.0 Hz, 1H), 3.10 (dd, J=12.5, 3.0 Hz, 1H), 3.73 (s, 2H), 3.81 (d, J=5.3 Hz, 2H), 4.04-4.12 (m, 1H), 7.75 (s, 2H), 7.80 (s, 1H).

Workup

  1. washwashed with 1 M aq. NaOH
  2. extractionThe washing is extracted back with EA
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product is purified by prep
  7. washHPLC (XBridge C18, 50×50 mm, 10 μm, eluting with a gradient of acetonitrile in water containing 0.5% of concentrated aq. ammonia)

Sources & evidence

ORD record
ord-1ca7a754468c4e74a92bf9f468abfd72
Source dataset
uspto-grants-2012_04
Patent number
US08148410B2

Reaction notes

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