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Diisopropylethylamine → [2-(2,5-Dichloro-phenoxy)-pyridin-3-yl]-(4-methylene-3,4-dihydro-2H-quinolin-1-yl)-methanone

HRID 1877394
ノート
印刷プレビュー

反応式

HRID 1877394 の反応式
C(O[C:6]([N:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11](=[CH2:18])[CH2:10][CH2:9]1)=[O:7])(C)(C)C.[Cl:19][C:20]1[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][C:21]=1[O:22][C:23]1[N:31]=[CH:30][CH:29]=[CH:28][C:24]=1C(O)=O.C(N(C(C)C)C(C)C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>Cl.O1CCOCC1>[Cl:19][C:20]1[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][C:21]=1[O:22][C:23]1[C:24]([C:6]([N:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11](=[CH2:18])[CH2:10][CH2:9]2)=[O:7])=[CH:28][CH:29]=[CH:30][N:31]=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

7

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 167959962-(2,5-Dichloro-phenoxy)-nicotinic acidHCID 67367966tert-butyl 4-methylene-3,4-dihydroquinoline-1(2H)-carboxylate

生成物 1

HCID 46195420
[2-(2,5-Dichloro-phenoxy)-pyridin-3-yl]-(4-methylene-3,4-dihydro-2H-quinolin-1-yl)-methanone
収率 7%

試薬・触媒・溶媒 2

HCID 313Hydrochloric Acid溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

A solution of 4-methylene-3,4-dihydro-2H-quinoline-1-carboxylic acid tert-butyl ester (44.2 mg, 0.18 mmol, 1.2 equiv) in 4 M HCl in dioxane (4 mL) was stirred at rt for 2 h. The solvent was removed under reduced pressure and the crude product redissolved in anhydrous DMF (1 mL). To this solution was added 2-(2,5-dichloro-phenoxy)-nicotinic acid (42.6 mg, 0.15 mmol, 1.0 equiv; Example 31, Step 1), N-ethyldiisopropylamine (97 mg, 131 μL, 0.75 mmol, 5.0 equiv; [CAS RN 7087-68-5]) and HATU (68 mg, 0.18 mmol, 1.2 equiv; [CAS RN 148893-10-1]) and the reaction mixture heated by microwave irradiation to 100° C. for 30 min. Removal of the solvent mixture under reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column equipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps, a Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water provided 4.1 mg (7%) of the title compound. MS (ISP): 410.7 [M+H]+.

後処理

  1. customThe solvent was removed under reduced pressure
  2. dissolutionthe crude product redissolved in anhydrous DMF (1 mL)
  3. customRemoval of the solvent mixture
  4. customunder reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column
  5. customequipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps
  6. washa Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water

出典と根拠

ORDレコード
ord-d088a38a50834ab99c31587c4c1d2348
出典データセット
uspto-grants-2012_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08309734B2

反応ノート

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