Diisopropylethylamine → tert-butyl 6-ethoxy-1-((4-(1-ethoxy-2-methylpropan-2-yl)-3,5-difluorophenyl)carbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

HRID 2202277ノート

反応式

HRID 2202277 の反応式
C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.[C:19]([O:23][C:24]([N:26]1[CH2:35][CH2:34][C:33]2[C:28](=[CH:29][CH:30]=[C:31]([O:36][CH2:37][CH3:38])[CH:32]=2)[CH:27]1[C:39]([OH:41])=O)=[O:25])([CH3:22])([CH3:21])[CH3:20].[CH2:42]([O:44][CH2:45][C:46]([C:49]1[C:55]([F:56])=[CH:54][C:52]([NH2:53])=[CH:51][C:50]=1[F:57])([CH3:48])[CH3:47])[CH3:43].CCN(C(C)C)C(C)C>CN(C1C=CN=CC=1)C.C(OCC)(=O)C.O>[CH2:37]([O:36][C:31]1[CH:32]=[C:33]2[C:28](=[CH:29][CH:30]=1)[CH:27]([C:39](=[O:41])[NH:53][C:52]1[CH:51]=[C:50]([F:57])[C:49]([C:46]([CH3:48])([CH3:47])[CH2:45][O:44][CH2:42][CH3:43])=[C:55]([F:56])[CH:54]=1)[N:26]([C:24]([O:23][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:25])[CH2:35][CH2:34]2)[CH3:38]

参加物

8

反応物 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 1186226932-(Tert-butoxycarbonyl)-6-ethoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acidHCID 1186227684-(1-Ethoxy-2-methylpropan-2-yl)-3,5-difluoroaniline

生成物 1

HCID 118622749tert-butyl 6-ethoxy-1-((4-(1-ethoxy-2-methylpropan-2-yl)-3,5-difluorophenyl)carbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate収率 50.2%

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
60 °C

実験手順

T3P (4.62 mL, 7.85 mmol) was added to a solution of 2-(tert-butoxycarbonyl)-6-ethoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid (841 mg, 2.62 mmol), 4-(1-ethoxy-2-methylpropan-2-yl)-3,5-difluoroaniline (600 mg, 2.62 mmol), DIEA (2.285 mL, 13.09 mmol) and DMAP (320 mg, 2.62 mmol) in ethyl acetate (5 mL), and the mixture was stirred at 60° C. overnight. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 3→50% ethyl acetate/hexane), and crystallized from ethyl acetate/hexane to give tert-butyl 6-ethoxy-1-((4-(1-ethoxy-2-methylpropan-2-yl)-3,5-difluorophenyl)carbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (700 mg, 1.314 mmol, 50.2%) as white crystals.

後処理

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography (solvent gradient; 3→50% ethyl acetate/hexane)
  6. customcrystallized from ethyl acetate/hexane

出典と根拠

ORDレコード
ord-8bb9a0cc47094b7695dfba37ec0e359c
出典データセット
uspto-grants-2016_06
特許番号
US09365520B2

反応ノート

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