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 1685792ノート

反応式

HRID 1685792 の反応式
[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]

参加物

4

反応物 2

HCID 222AmmoniaHCID 86646463HCID 86646463、化合物

生成物 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

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-50972b6a15824eb2add3c147b9a211b1
出典データセット
uspto-grants-2012_04
特許番号
US08148410B2

反応ノート

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