Diisopropylethylamine → N-[(2S)-3-(2-Ethyl-4-{5-[2-(1-ethyl-propyl)-6-methoxy-pyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-6-methyl-phenoxy)-2-hydroxy-propyl]-2-hydroxy-acetamide

HRID 245105ノート

反応式

HRID 245105 の反応式
[CH2:1]([CH:3]([C:6]1[CH:7]=[C:8]([CH:12]=[C:13]([O:15][CH3:16])[N:14]=1)[C:9]([OH:11])=O)[CH2:4][CH3:5])[CH3:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH2:48]([C:50]1[CH:65]=[C:64]([C:66](=[NH:69])[NH:67]O)[CH:63]=[C:62]([CH3:70])[C:51]=1[O:52][CH2:53][C@@H:54]([OH:61])[CH2:55][NH:56][C:57](=[O:60])[CH2:58][OH:59])[CH3:49]>CN(C=O)C.C1COCC1.CC(=O)OCC>[CH2:48]([C:50]1[CH:65]=[C:64]([C:66]2[N:69]=[C:9]([C:8]3[CH:12]=[C:13]([O:15][CH3:16])[N:14]=[C:6]([CH:3]([CH2:1][CH3:2])[CH2:4][CH3:5])[CH:7]=3)[O:11][N:67]=2)[CH:63]=[C:62]([CH3:70])[C:51]=1[O:52][CH2:53][C@@H:54]([OH:61])[CH2:55][NH:56][C:57](=[O:60])[CH2:58][OH:59])[CH3:49]

参加物

8

反応物 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 584181082-(1-Ethylpropyl)-6-methoxyisonicotinic acidHCID 178436630HCID 178436630、化合物

生成物 1

HCID 49871977N-[(2S)-3-(2-Ethyl-4-{5-[2-(1-ethyl-propyl)-6-methoxy-pyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-6-methyl-phenoxy)-2-hydroxy-propyl]-2-hydroxy-acetamide収率 45.6%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of 2-(1-ethyl-propyl)-6-methoxy-isonicotinic acid (200 mg, 770 μmol) in DMF (3 mL) and THF (10 mL), DIPEA (200 mg, 1.54 mmol) and TBTU (272 mg, 847 μmol) are added. The mixture is stirred at rt for 10 min before N—((S)-3-[2-ethyl-4-(N-hydroxycarbamimidoyl)-6-methyl-phenoxy]-2-hydroxy-propyl)-2-hydroxy-acetamide (251 mg, 770 μmol) is added. The mixture is stirred at rt for 30 min, diluted with EA (100 mL) and washed with brine. The org. extract is concentrated and the residue is dissolved in dioxane (50 mL). The mixture is stirred at 100° C. for 2 h before it is concentrated. The crude product is purified on prep. TLC plates using DCM containing 10% of methanol to give the title compound (180 mg) as a resin; LC-MS: tR=1.08 min, [M+H]+=513.13; 1H NMR (CDCl3): δ0.84 (t, J=7.3 Hz, 6H), 1.31 (t, J=7.5 Hz, 3H), 1.68-1.88 (m, 4H), 2.38 (s, 3H), 2.55-2.64 (m, 1H), 2.74 (q, J=7.5 Hz, 2H), 3.50-3.58 (m, 1H), 3.74-3.94 (m, 4H), 4.01 (s, 3H), 4.17-4.25 (m, 3H), 7.09 (t br, J=5.5 Hz, 1H), 7.31 (d, J=1.3 Hz, 1H), 7.43 (d, J=1.3 Hz, 1H), 7.86 (d, J=1.8 Hz), 7.88 (d, J=2.0 Hz).

後処理

  1. additionis added
  2. washwashed with brine
  3. extractionextract
  4. concentrationis concentrated
  5. dissolutionthe residue is dissolved in dioxane (50 mL)
  6. stirringThe mixture is stirred at 100° C. for 2 h before it
  7. concentrationis concentrated
  8. customThe crude product is purified on prep

出典と根拠

ORDレコード
ord-a8edd5b4253c41df88f5009f09215324
出典データセット
uspto-grants-2014_02
特許番号
US08658675B2

反応ノート

読み込み中…