Ammonia → (2S)-1-Amino-3-{4-[5-(5-diethylaminomethyl-4-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propan-2-ol

HRID 1685792Notes

Reaction equation

HRID 1685792 reaction equation
[CH2:1]([N:3]([CH2:30][CH3:31])[CH2:4][C:5]1[S:6][C:7]([C:11]2[O:15][N:14]=[C:13]([C:16]3[CH:21]=[C:20]([CH3:22])[C:19]([O:23][CH2:24][C@@H:25]4[CH2:27][O:26]4)=[C:18]([CH2:28][CH3:29])[CH:17]=3)[N:12]=2)=[CH:8][C:9]=1[CH3:10])[CH3:2].[NH3:32]>CO>[NH2:32][CH2:27][C@H:25]([OH:26])[CH2:24][O:23][C:19]1[C:20]([CH3:22])=[CH:21][C:16]([C:13]2[N:12]=[C:11]([C:7]3[S:6][C:5]([CH2:4][N:3]([CH2:30][CH3:31])[CH2:1][CH3:2])=[C:9]([CH3:10])[CH:8]=3)[O:15][N:14]=2)=[CH:17][C:18]=1[CH2:28][CH3:29]

Participants

4

Reactant 2

HCID 222AmmoniaHCID 86646463HCID 86646463, compound

Product 1

HCID 67265586(2S)-1-Amino-3-{4-[5-(5-diethylaminomethyl-4-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propan-2-ol

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

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. customThe solvent is evaporated
  2. customthe crude product is purified by prep
  3. additionThe product containing fractions
  4. filtrationare filtered over Amberlyst A21
  5. concentrationThe filtrate is concentrated
  6. customdried

Sources & evidence

ORD record
ord-50972b6a15824eb2add3c147b9a211b1
Source dataset
uspto-grants-2012_04
Patent number
US08148410B2

Reaction notes

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