Diisopropylethylamine → 1-{2-(Hex-5-enylmethylcarbamoyl)-4-[2-(6-methyl-2-pyridyl)-7-methoxy-8-methylquinolin-4-yloxy]cyclopentanecarbonyl}amino-2-vinylcyclopropanecarboxylic acid ethyl ester

HRID 531352ノート

反応式

HRID 531352 の反応式
[CH2:1]([O:3][C:4]([C:6]1([NH:11][C:12]([CH:14]2[CH2:18][CH:17]([O:19][C:20]3[C:29]4[C:24](=[C:25]([CH3:32])[C:26]([O:30][CH3:31])=[CH:27][CH:28]=4)[N:23]=C(C4C=CC=C(C)N=4)[CH:21]=3)[CH2:16][CH:15]2[C:40](O)=[O:41])=[O:13])[CH2:8][CH:7]1[CH:9]=[CH2:10])=[O:5])[CH3:2].Cl.[CH3:44][NH:45][CH2:46][CH2:47][CH2:48][CH2:49][CH:50]=[CH2:51].[CH:52]([N:55]([CH:58]([CH3:60])[CH3:59])CC)([CH3:54])[CH3:53].[CH3:61]N(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH2:1]([O:3][C:4]([C:6]1([NH:11][C:12]([CH:14]2[CH2:18][CH:17]([O:19][C:20]3[C:29]4[C:24](=[C:25]([CH3:32])[C:26]([O:30][CH3:31])=[CH:27][CH:28]=4)[N:23]=[C:60]([C:58]4[CH:59]=[CH:61][CH:54]=[C:52]([CH3:53])[N:55]=4)[CH:21]=3)[CH2:16][CH:15]2[C:40](=[O:41])[N:45]([CH2:46][CH2:47][CH2:48][CH2:49][CH:50]=[CH2:51])[CH3:44])=[O:13])[CH2:8][CH:7]1[CH:9]=[CH2:10])=[O:5])[CH3:2]

参加物

6

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 668720342-(1-Ethoxycarbonyl-2-vinylcyclopropylcarbamoyl)-4-[2-(6-methyl-2-pyridyl)-7-methoxy-8-methylquinolin-4-yloxy]cyclopentanecarboxylic acidHCID 71413963N-Methylhex-5-en-1-amine hydrochloride

生成物 1

HCID 668720481-{2-(Hex-5-enylmethylcarbamoyl)-4-[2-(6-methyl-2-pyridyl)-7-methoxy-8-methylquinolin-4-yloxy]cyclopentanecarbonyl}amino-2-vinylcyclopropanecarboxylic acid ethyl ester収率 82%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A solution of 2-(1-ethoxycarbonyl-2-vinylcyclopropylcarbamoyl)-4-[2-(6-methyl-2-pyridyl)-7-methoxy-8-methylquinolin-4-yloxy]cyclopentanecarboxylic acid (99, 0.77 g, 1.344 mmol), N-methylhex-5-enylamine hydrochloride (221 mg, 1.95 mmol) and diisopropylethylamine (1.17 mL, 6.72 mmol) in DMF (25 mL) was stirred at 0° C. under inert atmosphere. After 30 min HATU (741 mg, 1.95 mmol) was added and the reaction mixture was allowed to warm up to room temperature overnight. Then, DMF was evaporated and the residue was partitioned between AcOEt and a solution of NaHCO3. Organic layer was successively washed with water and brine, dried (MgSO4), filtered and evaporated. The crude product was purified by silica gel chromatography (gradient Heptane/AcOEt 80:20 to 50:50) to give 735 mg (82%) of the title compound: m/z=669 (M+H)+.

後処理

  1. customThen, DMF was evaporated
  2. customthe residue was partitioned between AcOEt
  3. washOrganic layer was successively washed with water and brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude product was purified by silica gel chromatography (gradient Heptane/AcOEt 80:20 to 50:50)

出典と根拠

ORDレコード
ord-e4154a1c1f584fefa839da8dac365dac
出典データセット
uspto-grants-2016_05
特許番号
US09353103B2

反応ノート

読み込み中…