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Dimethylformamide → tert-Butyl 4-(1-(3-(((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-2-methyl-1H-indol-1-yl)ethyl)piperidine-1-carboxylate

HRID 2206529
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HRID 2206529 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]([N:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:18]([C:25](O)=[O:26])=[C:17]2[CH3:28])[CH3:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[NH2:30][CH2:31][C:32]1[C:33](=[O:41])[NH:34][C:35]([CH3:40])=[CH:36][C:37]=1[O:38][CH3:39].CN(C=O)C.CCN(C(C)C)C(C)C.CCOC(C(C#N)=NOC(N1CCOCC1)=[N+](C)C)=O.F[P-](F)(F)(F)(F)F>O>[CH3:39][O:38][C:37]1[CH:36]=[C:35]([CH3:40])[NH:34][C:33](=[O:41])[C:32]=1[CH2:31][NH:30][C:25]([C:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[N:16]([CH:14]([CH:11]2[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:7])[CH2:13][CH2:12]2)[CH3:15])[C:17]=1[CH3:28])=[O:26]
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참가 물질

7

반응물 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 75951468(1-Cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphateHCID 89740341HCID 89740341, 화합물HCID 1177807191H-Indole-3-carboxylic acid, 1-[1-[1-[(1,1-dimethylethoxy)carbonyl]-4-piperidinyl]ethyl]-2-methyl-

생성물 1

HCID 117807734
tert-Butyl 4-(1-(3-(((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-2-methyl-1H-indol-1-yl)ethyl)piperidine-1-carboxylate
수율 65.3%

시약·촉매·용매 1

HCID 962Water용매

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온도
0 °C

실험 절차

A 250 mL round bottom flask was charged with a magnetic stir bar, (R or S)-1-(1-(1-(tert-butoxycarbonyl)piperidin-4-yl)ethyl)-2-methyl-1H-indole-3-carboxylic acid (1.950 g, 5.05 mmol), 3-(aminomethyl)-4-methoxy-6-methylpyridin-2(1H)-one hydrochloride (2.065 g, 10.09 mmol), DMF (25.2 ml, 5.05 mmol), Hunig's base (3.52 ml, 20.18 mmol). The reaction mixture was cooled to 0° C. and COMU (2.16 g, 5.05 mmol) was added. The reaction was allowed to stir overnight to room temperature. The reaction mixture was diluted with water and extracted with EtOAc. The combined organic extract was washed with brine, dried with MgSO4, filtered and conc., in vacuo to afford the crude material which was purified via silica gel chromatography (120 g) using MeOH/ethyl acetate (1:5) as eluent to afford the title compound (1.86 g, 3.29 mmol, 65.3% yield). LCMS 537 (M+1)+ 1H NMR (400 MHz, DMSO-d6) δ=11.83-11.71 (m, 1H), 7.80 (br. s., 1H1), 7.73 (d, J=7.6 Hz, 1H), 7.62 (d, J=7.8 Hz, 1H), 7.06 (td, J=7.1, 14.4 Hz, 2H), 6.21 (s, 1H), 4.32 (br. s., 2H), 4.16 (br. s., 1H), 4.02 (br. s., 1H), 3.85 (s, 3H), 3.75 (br. s., 1H), 2.70 (br. s., 1H), 2.58 (s, 3H), 2.37 (br. s., 1H), 2.21 (s, 3H), 1.90 (d, J=12.9 Hz, 1H), 1.53 (d, J=6.9 Hz, 3H), 1.35 (s, 10H), 1.21 (br. s., 1H), 0.89 (d, J=8.7 Hz, 1H), 0.67 (d, J=11.8 Hz, 1H).

후처리

  1. additionA 250 mL round bottom flask was charged with a magnetic stir bar
  2. extractionextracted with EtOAc
  3. extractionThe combined organic extract
  4. washwas washed with brine
  5. dry with materialdried with MgSO4
  6. filtrationfiltered
  7. customconc., in vacuo to afford the crude material which
  8. customwas purified via silica gel chromatography (120 g)

출처 및 근거

ORD 기록
ord-3e78289d1b0541e69d93ecfe9082a68a
출처 데이터셋
uspto-grants-2016_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09371331B2

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