Diisopropylethylamine → 2,6-dichloro-N-(tetrahydro-2H-pyran-4-yl)nicotinamide

HRID 1187379노트

반응식

HRID 1187379 반응식
[Cl:1][C:2]1[N:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:3]=1[C:4](Cl)=[O:5].[NH2:12][CH:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1.C(N(C(C)C)C(C)C)C>C(Cl)Cl>[Cl:1][C:2]1[N:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:3]=1[C:4]([NH:12][CH:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1)=[O:5]

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 4192234-AminotetrahydropyranHCID 122639842,6-Dichlorpyridine-3-carbonyl chloride

생성물 1

HCID 598306882,6-dichloro-N-(tetrahydro-2H-pyran-4-yl)nicotinamide수율 92%

시약·촉매·용매 1

HCID 6344Dichloromethane용매3회

실험 절차

A solution of 2,6-dichloronicotinoyl chloride (4.21 g, 20 mmol) in DCM (20 mL) was added dropwise to a stirred suspension of 4-aminotetrahydropyran (2.03 g, 20 mmol) and N-ethyldiisopropylamine (4.19 mL, 24 mmol) in DCM (20 mL) at 0° C., over a period of 30 minutes under nitrogen. The resulting suspension was stirred at room temperature for 18 hours. The reaction mixture was diluted with DCM (200 mL), and washed sequentially with water (50 mL) and saturated brine (50 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in DCM. Pure fractions were evaporated to dryness to afford 2,6-dichloro-N-(tetrahydro-2H-pyran-4-yl)nicotinamide (5.03 g, 92%) as a white solid.

후처리

  1. washwashed sequentially with water (50 mL) and saturated brine (50 mL)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. customto afford crude product
  6. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in DCM
  7. customPure fractions were evaporated to dryness

출처 및 근거

ORD 기록
ord-805d32d8001d42c6869f678b2b9cfb1a
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08673938B2

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