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Potassium Carbonate → Tert-butyl (1-{5-chloro-4-cyano-2-ethoxy-3-[5-(methylsulfonyl)pyridin-3-yl]phenyl}ethyl)carbamate

HRID 510993
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HRID 510993 반응식
Br[C:2]1[C:3]([O:21][CH2:22][CH3:23])=[C:4]([CH:11]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH3:12])[CH:5]=[C:6]([Cl:10])[C:7]=1[C:8]#[N:9].[CH3:24][S:25]([C:28]1[CH:29]=[N:30][CH:31]=[C:32](B2OC(C)(C)C(C)(C)O2)[CH:33]=1)(=[O:27])=[O:26].C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:10][C:6]1[C:7]([C:8]#[N:9])=[C:2]([C:32]2[CH:31]=[N:30][CH:29]=[C:28]([S:25]([CH3:24])(=[O:27])=[O:26])[CH:33]=2)[C:3]([O:21][CH2:22][CH3:23])=[C:4]([CH:11]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH3:12])[CH:5]=1
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참가 물질

7

반응물 3

HCID 11430Potassium CarbonateHCID 533985305-(Methylsulfonyl)pyridine-3-boronic acid pinacol esterHCID 123418761Tert-butyl[1-(3-bromo-5-chloro-4-cyano-2-ethoxyphenyl)ethyl]carbamate

생성물 1

HCID 86666906Tert-butyl (1-{5-chloro-4-cyano-2-ethoxy-3-[5-(methylsulfonyl)pyridin-3-yl]phenyl}ethyl)carbamate수율 62.5%

시약·촉매·용매 3

HCID 178418397
HCID 178418397, 화합물
촉매
HCID 962Water용매
HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

To tert-butyl [-1-(3-bromo-5-chloro-4-cyano-2-ethoxyphenyl)ethyl]carbamate (50 mg, 0.1 mmol, from Example 179, Step 3) and 3-(methylsulfonyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (30. mg, 0.11 mmol, Peptech, catalog #BE358) in 1,4-dioxane (4 mL) was added potassium carbonate (30 mg, 0.2 mmol) in water (2 mL). The reaction was degassed with N2. Tetrakis(triphenylphosphine)palladium(0) (40 mg, 0.04 mmol) was added and degassed again with N2. The reaction was heated at 100° C. overnight. The reaction was allowed to cool to room temperature and was partitioned between EtOAc and water. The combined organic layer was washed with brine, dried over MgSO4, filtered and concentrated to give crude product. The product was purified by chromatography on silica gel eluting with a hexane:EtOAc gradient to give tert-butyl (1-{5-chloro-4-cyano-2-ethoxy-3-[5-(methylsulfonyl)pyridin-3-yl]phenyl}ethyl)carbamate as a yellow oil (0.030 g, 60%). LCMS calculated for C22H27ClN3O5S (M+H)+: m/z=480.1. found: 480.1.

후처리

  1. customThe reaction was degassed with N2
  2. customdegassed again with N2
  3. temperatureto cool to room temperature
  4. customwas partitioned between EtOAc and water
  5. washThe combined organic layer was washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give crude product
  10. customThe product was purified by chromatography on silica gel eluting with a hexane

출처 및 근거

ORD 기록
ord-3c8db229de9f4117bfb20e52539c43fa
출처 데이터셋
uspto-grants-2015_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09096600B2

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