Diisopropylethylamine → (2S,4R)-methyl 4-((3-chloro-7-methoxyquinoxalin-2-yl)oxy)-1-((S)-3,3-dimethyl-2-((((1R,2R)-2-(pent-4-en-1-yl)cyclopropoxy)carbonyl)amino)butanoyl)pyrrolidine-2-carboxylate

HRID 659828ノート

反応式

HRID 659828 の反応式
Cl.[Cl:2][C:3]1[C:4]([O:15][C@H:16]2[CH2:20][NH:19][C@H:18]([C:21]([O:23][CH3:24])=[O:22])[CH2:17]2)=[N:5][C:6]2[C:11]([N:12]=1)=[CH:10][CH:9]=[C:8]([O:13][CH3:14])[CH:7]=2.[CH3:25][C:26]([CH3:44])([CH3:43])[C@@H:27]([C:40](O)=[O:41])[NH:28][C:29]([O:31][C@@H:32]1[CH2:34][C@H:33]1[CH2:35][CH2:36][CH2:37][CH:38]=[CH2:39])=[O:30].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[CH3:25][C:26]([CH3:44])([CH3:43])[C@@H:27]([C:40]([N:19]1[CH2:20][C@H:16]([O:15][C:4]2[C:3]([Cl:2])=[N:12][C:11]3[C:6](=[CH:7][C:8]([O:13][CH3:14])=[CH:9][CH:10]=3)[N:5]=2)[CH2:17][C@H:18]1[C:21]([O:23][CH3:24])=[O:22])=[O:41])[NH:28][C:29]([O:31][C@@H:32]1[CH2:34][C@H:33]1[CH2:35][CH2:36][CH2:37][CH:38]=[CH2:39])=[O:30]

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 59287076L-Valine, 3-methyl-N-[[[(1R,2R)-2-(4-penten-1-yl)cyclopropyl]oxy]carbonyl]-HCID 78358295Methyl (2S)-4-((3-chloro-7-methoxyquinoxalin-2-yl)oxy)pyrrolidine-2-carboxylate hydrochloride

生成物 1

HCID 78358296(2S,4R)-methyl 4-((3-chloro-7-methoxyquinoxalin-2-yl)oxy)-1-((S)-3,3-dimethyl-2-((((1R,2R)-2-(pent-4-en-1-yl)cyclopropoxy)carbonyl)amino)butanoyl)pyrrolidine-2-carboxylate収率 96%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
20 °C

実験手順

A solution (0.2 M) of methyl (4R)-4-[(3-chloro-7-methoxyquinoxalin-2-yl)oxy]-L-prolinate hydrochloride in DMF was treated with 3-methyl-N-({[(1R,2R)-2-pent-4-en-1-ylcyclopropyl]oxy}carbonyl)-L-valine (1.1 eq), DIEA (5 eq) and HATU (1.2 eq). The resulting mixture was stirred at 20° C. for 5 h, then diluted with EtOAc. The organic layer was separated and washed with aqueous HCl (1 N), saturated aqueous NaHCO3 and brine. The dried organic phase was concentrated under reduced pressure to give a residue that was purified by flash chromatography (eluent 10-30% EtOAc/petroleum ether) to furnish the title compound (96%) as an oil. MS (ES+) m/z 604 (M+H)+

後処理

  1. customThe organic layer was separated
  2. washwashed with aqueous HCl (1 N), saturated aqueous NaHCO3 and brine
  3. concentrationThe dried organic phase was concentrated under reduced pressure
  4. customto give a residue that
  5. customwas purified by flash chromatography (eluent 10-30% EtOAc/petroleum ether)

出典と根拠

ORDレコード
ord-564de583833948feb3a913c56edcf3dd
出典データセット
uspto-grants-2011_12
特許番号
US08080654B2

反応ノート

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