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1,4-Dioxane → Benzyl [2-({[4-((3R,4R,5S)-3-[(tert-butoxycarbonyl)amino]-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methylpiperidin-1-yl)pyridin-3-yl]amino}carbonyl)-7-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)quinolin-3-yl]carbamate

HRID 924474
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인쇄 미리보기

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HRID 924474 반응식
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:44][C:45](=[O:54])[O:46][CH2:47][C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)[C:8]([C:12]([NH:14][C:15]3[CH:16]=[N:17][CH:18]=[CH:19][C:20]=3[N:21]3[CH2:26][C@H:25]([CH3:27])[C@@H:24]([O:28][Si:29]([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30])[C@H:23]([NH:36][C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:22]3)=[O:13])=[N:9]2)=[CH:4][CH:3]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1.[CH3:69][N:70]1[CH2:75][CH:74]=[C:73](B2OC(C)(C)C(C)(C)O2)[CH2:72][CH2:71]1>C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.NC1C=CC=CC=1C1C=CC=CC=1[Pd]Cl.O>[C:40]([O:39][C:37]([NH:36][C@H:23]1[C@H:24]([O:28][Si:29]([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30])[C@@H:25]([CH3:27])[CH2:26][N:21]([C:20]2[CH:19]=[CH:18][N:17]=[CH:16][C:15]=2[NH:14][C:12]([C:8]2[C:7]([NH:44][C:45](=[O:54])[O:46][CH2:47][C:48]3[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=3)=[CH:6][C:5]3[C:10](=[CH:11][C:2]([C:73]4[CH2:72][CH2:71][N:70]([CH3:69])[CH2:75][CH:74]=4)=[CH:3][CH:4]=3)[N:9]=2)=[O:13])[CH2:22]1)=[O:38])([CH3:41])([CH3:42])[CH3:43]
참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트

참가 물질

7

반응물 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 207733711-Methyl-1,2,3,6-tetrahydropyridine-4-boronic acid, pinacol esterHCID 86726916Benzyl [7-bromo-2-({[4-((3R,4R,5S)-3-[(tert-butoxycarbonyl)amino]-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methylpiperidin-1-yl)pyridin-3-yl]amino}carbonyl)quinolin-3-yl]carbamate

생성물 1

HCID 86726919
Benzyl [2-({[4-((3R,4R,5S)-3-[(tert-butoxycarbonyl)amino]-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methylpiperidin-1-yl)pyridin-3-yl]amino}carbonyl)-7-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)quinolin-3-yl]carbamate
수율 36.2%

시약·촉매·용매 2

HCID 178439015HCID 178439015, 화합물촉매HCID 962Water용매

반응 조건

온도
90 °C

실험 절차

A pressure vial was charged with benzyl [7-bromo-2-({[4-((3R,4R,5S)-3-[(tert-butoxycarbonyl)amino]-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methylpiperidin-1-yl)pyridin-3-yl]amino}carbonyl)quinolin-3-yl]carbamate (0.035 g, 0.043 mmol), K3PO4 (0.0181 g, 0.0852 mmol), 1,4-dioxane (0.55 mL), water (0.092 mL) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine (0.014 g, 0.063 mmol). The mixture was deoxygenated with nitrogen for 10 min. Dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine-(2′-aminobiphenyl-2-yl)(chloro)palladium (1:1) (0.0022 g, 0.0028 mmol) was added. The mixture was sealed with screw cap, then heated at 90° C. for 1.5 h. The mixture was quenched with water, extracted with EtOAc. The combined organic extracts were dried and concentrated under reduced pressure. The residue was purified by flash chromatography on 20 g silica gel, eluting with 0-100% EtOAc in hexanes, to give the sub-title compound (0.013 g, 36%). LCMS calc. for C46H62N7O6Si [M+H]+: m/z=836.5. found: 836.6.

후처리

  1. customThe mixture was deoxygenated with nitrogen for 10 min
  2. customThe mixture was sealed with screw
  3. customcap
  4. customThe mixture was quenched with water
  5. extractionextracted with EtOAc
  6. customThe combined organic extracts were dried
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by flash chromatography on 20 g silica gel
  9. washeluting with 0-100% EtOAc in hexanes

출처 및 근거

ORD 기록
ord-73df218cb7534260a28f29cf3cad0343
출처 데이터셋
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09278950B2

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