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

HRID 2202272노트

반응식

HRID 2202272 반응식
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].[F:42][C:43]1[CH:44]=[C:45]([CH:47]=[C:48]([F:56])[C:49]=1[C:50]([CH3:55])([CH3:54])[CH2:51][O:52][CH3:53])[NH2:46].CCN(C(C)C)C(C)C>CN(C1C=CN=CC=1)C.C(OCC)(=O)C.O>[F:42][C:43]1[CH:44]=[C:45]([NH:46][C:39]([CH:27]2[C:28]3[C:33](=[CH:32][C:31]([O:36][CH2:37][CH3:38])=[CH:30][CH:29]=3)[CH2:34][CH2:35][N:26]2[C:24]([O:23][C:19]([CH3:20])([CH3:22])[CH3:21])=[O:25])=[O:41])[CH:47]=[C:48]([F:56])[C:49]=1[C:50]([CH3:54])([CH3:55])[CH2:51][O:52][CH3:53]

참가 물질

8

반응물 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 1186226932-(Tert-butoxycarbonyl)-6-ethoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acidHCID 1186228033,5-Difluoro-4-(1-methoxy-2-methylpropan-2-yl)aniline

생성물 1

HCID 118622717tert-butyl 1-((3,5-difluoro-4-(1-methoxy-2-methylpropan-2-yl)phenyl)carbamoyl)-6-ethoxy-3,4-dihydroisoquinoline-2(1H)-carboxylate수율 82%

시약·촉매·용매 3

HCID 142844-(Dimethylamino)pyridine촉매HCID 962Water용매HCID 8857Ethyl Acetate용매

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온도
60 °C

실험 절차

T3P (9.88 mL, 16.80 mmol) was added to a solution of 2-(tert-butoxycarbonyl)-6-ethoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid (1.8 g, 5.60 mmol), 3,5-difluoro-4-(1-methoxy-2-methylpropan-2-yl)aniline (1.206 g, 5.60 mmol), DIEA (4.89 mL, 28.01 mmol) and DMAP (0.684 g, 5.60 mmol) in ethyl acetate (5 mL), and the mixture was stirred overnight at 60° C. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with 10% aqueous citric acid solution, aqueous sodium hydrogencarbonate solution and 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) to give tert-butyl 1-((3,5-difluoro-4-(1-methoxy-2-methylpropan-2-yl)phenyl)carbamoyl)-6-ethoxy-3,4-dihydroisoquinoline-2(1H)-carboxylate (2.380 g, 4.59 mmol, 82%) as a white solid.

후처리

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with 10% aqueous citric acid solution, aqueous sodium hydrogencarbonate solution and 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)

출처 및 근거

ORD 기록
ord-12621204e001486ab13651f53a115d3d
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09365520B2

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