Triethylamine → 5-((E)-2-{2-[(R)-1-({(S)-1-[(S)-2-(2-cyclopropyl-2-hydroxy-acetylamino)-propionyl]-hexahydro-pyridazine-3-carbonyl}-amino)-ethyl]-quinolin-7-yl}-vinyl)-[1,3]dioxane-5-carboxylic acid

HRID 2176264ノート

反応式

HRID 2176264 の反応式
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([C@H:12]([NH:14][C:15]([C@@H:17]3[CH2:22][CH2:21][CH2:20][N:19]([C:23](=[O:34])[C@@H:24]([NH:26][C:27](=[O:33])[CH:28]([CH:30]4[CH2:32][CH2:31]4)[OH:29])[CH3:25])[NH:18]3)=[O:16])[CH3:13])=[N:9]2)=[CH:4][CH:3]=1.[CH:35]([C:37]1([C:43]([OH:45])=[O:44])[CH2:42][O:41][CH2:40][O:39][CH2:38]1)=[CH2:36].C(N(CC)CC)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:30]1([CH:28]([OH:29])[C:27]([NH:26][C@@H:24]([CH3:25])[C:23]([N:19]2[CH2:20][CH2:21][CH2:22][C@@H:17]([C:15]([NH:14][C@@H:12]([C:8]3[CH:7]=[CH:6][C:5]4[C:10](=[CH:11][C:2](/[CH:36]=[CH:35]/[C:37]5([C:43]([OH:45])=[O:44])[CH2:42][O:41][CH2:40][O:39][CH2:38]5)=[CH:3][CH:4]=4)[N:9]=3)[CH3:13])=[O:16])[NH:18]2)=[O:34])=[O:33])[CH2:32][CH2:31]1

参加物

7

反応物 4

HCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 867060855-Vinyl[1,3]dioxane-5-carboxylic acidHCID 86706105(S)-1-[(S)-2-(2-cyclopropyl-2-hydroxy-acetylamino)-propionyl]-hexahydro-pyridazine-3-carboxylic acid [(R)-1-(7-bromo-quinolin-2-yl)-ethyl]-amide

生成物 1

HCID 867061045-((E)-2-{2-[(R)-1-({(S)-1-[(S)-2-(2-cyclopropyl-2-hydroxy-acetylamino)-propionyl]-hexahydro-pyridazine-3-carbonyl}-amino)-ethyl]-quinolin-7-yl}-vinyl)-[1,3]dioxane-5-carboxylic acid

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
50 °C

実験手順

A solution of (S)-1-[(S)-2-(2-cyclopropyl-2-hydroxy-acetylamino)-propionyl]-hexahydro-pyridazine-3-carboxylic acid [(R)-1-(7-bromo-quinolin-2-yl)-ethyl]-amide (592 mg, 1.11 mmol), 5-vinyl[1,3]dioxane-5-carboxylic acid (176 mg, 1.11 mmol), triethylamine (343 mg, 472 μL, 3.39 mmol) and tri(o-tolyl)phosphine (67 mg, 0.22 mmol) in 1,4-dioxane (15 mL) was degassed with nitrogen for 5 minutes and then warmed to 50° C. under nitrogen with stirring. Tris(dibenzylideneacetone)dipalladium(0) (101 mg, 0.11 mmol) was added and the mixture was heated to reflux for 20 minutes and then allowed to cool to room temperature. The suspension was filtered through Celite and the filtrate evaporated to give crude 5-((E)-2-{2-[(R)-1-({(S)-1-[(S)-2-(2-cyclopropyl-2-hydroxy-acetylamino)-propionyl]-hexahydro-pyridazine-3-carbonyl}-amino)-ethyl]-quinolin-7-yl}-vinyl)-[1,3]dioxane-5-carboxylic acid.

後処理

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 20 minutes
  3. temperatureto cool to room temperature
  4. filtrationThe suspension was filtered through Celite
  5. customthe filtrate evaporated

出典と根拠

ORDレコード
ord-a64361faa45045c9ae34061ae64ebc2a
出典データセット
uspto-grants-2015_06
特許番号
US09062092B2

反応ノート

読み込み中…