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Dimethyl Sulfoxide → N-(6-methoxypyrazin-2-yl)-4-(3-{[5-(trifluoromethyl)pyridin-2-yl]oxy}benzylidene)piperidine-1-carboxamide

HRID 1666358
ノート
印刷プレビュー

反応式

HRID 1666358 の反応式
Cl.N1C[CH2:6][C:5](=[C:8]2[CH:24]=[CH:23][CH:22]=[C:10]([O:11][C:12]3[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][N:13]=3)[CH:9]2C)CC1.[CH3:26][O:27][C:28]1[N:33]=[C:32]([NH:34]C(=O)OC2C=CC=CC=2)[CH:31]=[N:30][CH:29]=1.[CH:44]([N:47]([CH:50]([CH3:52])C)[CH2:48][CH3:49])(C)C.CS(C)=[O:55]>>[CH3:26][O:27][C:28]1[N:33]=[C:32]([NH:34][C:44]([N:47]2[CH2:48][CH2:49][C:6](=[CH:5][C:8]3[CH:24]=[CH:23][CH:22]=[C:10]([O:11][C:12]4[CH:17]=[CH:16][C:15]([C:18]([F:19])([F:20])[F:21])=[CH:14][N:13]=4)[CH:9]=3)[CH2:52][CH2:50]2)=[O:55])[CH:31]=[N:30][CH:29]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 4

HCID 679Dimethyl SulfoxideHCID 81531DiisopropylethylamineHCID 66875760Phenyl (6-methoxypyrazin-2-yl)carbamateHCID 668763562-(3-Piperidin-4-ylidene-methyl-phenoxy)-5-trifluoromethyl-pyridine hydrochloride

生成物 1

HCID 24963360N-(6-methoxypyrazin-2-yl)-4-(3-{[5-(trifluoromethyl)pyridin-2-yl]oxy}benzylidene)piperidine-1-carboxamide収率 69%

反応条件

温度
60 °C

実験手順

A solution of 2-(3-piperidin-4-ylidene-methyl-phenoxy)-5-trifluoromethyl-pyridine hydrochloride (0.371 g, 1.00 mmol) (from Example 1, Step 5) and phenyl 6-methoxypyrazin-2-ylcarbamate (0.245 g, 1.00 mmol, from Step 1) in DMSO (2.5 mL) was treated with diisopropylethylamine (0.155 g, 1.2 mmol) and heated to 60° C. After 3 h, the reaction mixture was partitioned between water and ethyl acetate. The organic layer was separated and the aqueous layer was extracted again with ethyl acetate. The combined organic layers were washed with brine and dried over sodium sulfate, filtered and concentrated. The residue was crystallized in a 1:1 mix of hexanes and ethyl ether to afford the title compound (310 mg, 69%) as white crystals. MS (APCI 10 V) AP+ 486.20; 1H NMR (400 MHz, DMSO-d6) δ ppm 2.33 (t, J=5.46 Hz, 2H) 2.44 (t, J=5.46 Hz, 2H) 3.46 (t, J=5.46 Hz, 2H) 3.55 (t, J=5.46 Hz, 2H) 3.86 (s, 3H) 6.37 (s, 1H) 7.02-7.04 (m, 2H) 7.10 (d, J=7.62 Hz, 1H) 7.20 (d, J=8.60, Hz, 1H) 7.38 (t, J=8.77 Hz, 1H) 7.81 (s, 1H) 8.20 (dd, J=8.59 Hz, 2.14 Hz, 1H) 8.55 (s, 1H) 8.58 (s, 1H) 9.25 (s, 1H).

後処理

  1. customthe reaction mixture was partitioned between water and ethyl acetate
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted again with ethyl acetate
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was crystallized in a 1:1
  9. additionmix of hexanes and ethyl ether

出典と根拠

ORDレコード
ord-352ce4750d254ea3a9067945ebb4aee7
出典データセット
uspto-grants-2011_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08044052B2

反応ノート

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