Methylamine → 3-{2-ethyl-4-[5-(2-ethyl-6-methyl-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenyl}-N-methyl-propionamide

HRID 2040822ノート

反応式

HRID 2040822 の反応式
[CH2:1]([C:3]1[CH:8]=[C:7]([C:9]2[N:13]=[C:12]([C:14]3[CH:19]=[C:18]([CH3:20])[N:17]=[C:16]([CH2:21][CH3:22])[CH:15]=3)[O:11][N:10]=2)[CH:6]=[C:5]([CH3:23])[C:4]=1[CH2:24][CH2:25][C:26]([OH:28])=O)[CH3:2].C[CH2:30][N:31](C(C)C)C(C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CN>CN(C=O)C.C1COCC1>[CH2:1]([C:3]1[CH:8]=[C:7]([C:9]2[N:13]=[C:12]([C:14]3[CH:19]=[C:18]([CH3:20])[N:17]=[C:16]([CH2:21][CH3:22])[CH:15]=3)[O:11][N:10]=2)[CH:6]=[C:5]([CH3:23])[C:4]=1[CH2:24][CH2:25][C:26]([NH:31][CH3:30])=[O:28])[CH3:2]

参加物

7

反応物 4

HCID 6329MethylamineHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 592347473-{2-Ethyl-4-[5-(2-ethyl-6-methyl-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenyl}-propionic acid

生成物 1

HCID 592347563-{2-ethyl-4-[5-(2-ethyl-6-methyl-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenyl}-N-methyl-propionamide収率 77.5%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 3-{2-ethyl-4-[5-(2-ethyl-6-methyl-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenyl}-propionic acid (26 mg, 69 μmol) and DIPEA (27 mg, 207 μmol) in DMF (3 mL) is added PyBOP (40 mg, 76 μmol) at 0° C. The mixture is stirred for 15 min at 0° C. before methylamine (2.4 mg, 76 μmol, 38 μL of a 2 M solution in THF) is added. Stirring is continued for 1 h at 0° C. The reaction is quenched with water (2 mL), and the mixture is diluted with sat. aq. NaHCO3 solution. The mixture is extracted twice with ether. The combined org. extracts are dried over MgSO4, filtered and concentrated. The crude product is purified on prep. TLC plates with heptane:EA 1:4 to give 3-{2-ethyl-4-[5-(2-ethyl-6-methyl-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenyl}-N-methyl-propionamide (21 mg) as a white solid; LC-MS: tR=0.90 min; [M+1]+=393.45; 1H NMR δ 1.32 (t, J=7.5 Hz, 3 H), 1.40 (t, J=7.8 Hz, 3 H), 2.34-2.41 (m, 2 H), 2.45 (s, 3 H), 2.69 (s, 3 H), 2.77 (q, J=7.5 Hz, 2 H), 2.85 (d, J=4.8 Hz, 3 H), 2.95 (q, J=7.8 Hz, 2 H), 3.07-3.13 (m, 2H), 5.41 (s br, 1 H), 7.76 (s, 2 H), 7.84 (s, 1 H), 7.86 (s, 1 H).

後処理

  1. additionis added
  2. customThe reaction is quenched with water (2 mL)
  3. additionthe mixture is diluted with sat. aq. NaHCO3 solution
  4. extractionThe mixture is extracted twice with ether
  5. dry with materialextracts are dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product is purified on prep

出典と根拠

ORDレコード
ord-72b0696b8284431494c3d18663c94701
出典データセット
uspto-grants-2013_11
特許番号
US08580824B2

反応ノート

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