Methyl iodide → 6-[(3-{[Tert-butyl(dimethyl)silyl]oxy}propyl)(methyl)amino]-2-chloro-5-fluoronicotinonitrile

HRID 603472노트

반응식

HRID 603472 반응식
[H-].[Na+].[Si:3]([O:10][CH2:11][CH2:12][CH2:13][NH:14][C:15]1[C:22]([F:23])=[CH:21][C:18]([C:19]#[N:20])=[C:17]([Cl:24])[N:16]=1)([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:5])[CH3:4].[CH3:25]I>CN(C=O)C>[Si:3]([O:10][CH2:11][CH2:12][CH2:13][N:14]([CH3:25])[C:15]1[C:22]([F:23])=[CH:21][C:18]([C:19]#[N:20])=[C:17]([Cl:24])[N:16]=1)([C:6]([CH3:8])([CH3:9])[CH3:7])([CH3:5])[CH3:4]

참가 물질

5

반응물 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 866045976-[(3-{[Tert-butyl(dimethyl)silyl]oxy}propyl)amino]-2-chloro-5-fluoronicotinonitrile

생성물 1

HCID 866045996-[(3-{[Tert-butyl(dimethyl)silyl]oxy}propyl)(methyl)amino]-2-chloro-5-fluoronicotinonitrile수율 105.5%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

Sodium hydride (0.11 g, 4.65 mmol) was added to a solution of 6-[(3-{[tert-butyl(dimethyl)-I4-silyl]oxy}propyl)amino]-2-chloro-5-fluoronicotinonitrile (Example 309, 0.80 g, 2.33 mmol) in DMF (23.26 mL). The mixture was stirred at rt for 30 min, and then MeI (0.58 mL, 9.30 mmol) added. The reaction mixture was stirred at rt for 18 h, quenched with water, and the aqueous phase was extracted with ether. The combined ether extracts were washed with water, brine, and then dried (MgSO4), filtered, and concentrated under reduced pressure. The product (0.88 g, 99%) was isolated after silica gel flash chromatography (2:1 hexanes/EtOAc). 1H NMR (400 MHz, CD3OD) δ 7.53 (d, 1H), 3.70-3.60 (m, 4H), 3.17 (d, 3H), 1.84-1.76 (m, 2H), 0.84 (s, 9H), 0.00 (s, 6H).

후처리

  1. stirringThe reaction mixture was stirred at rt for 18 h
  2. customquenched with water
  3. extractionthe aqueous phase was extracted with ether
  4. washThe combined ether extracts were washed with water, brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-cfaff047b4754e808ae4235074524778
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07906653B2

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