Pyridine → 4-{[(3,5-dimethyl-4-isoxazolyl)methyl]oxy}-N-{2-methyl-6-[1-(phenylmethyl)-3-pyrrolidinyl]-3-pyridinyl}benzenesulfonamide

HRID 594135노트

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HRID 594135 반응식
[CH3:1][C:2]1[C:7]([NH2:8])=[CH:6][CH:5]=[C:4]([CH:9]2[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH2:10]2)[N:3]=1.N1C=CC=CC=1.[CH3:27][C:28]1[C:32]([CH2:33][O:34][C:35]2[CH:40]=[CH:39][C:38]([S:41](Cl)(=[O:43])=[O:42])=[CH:37][CH:36]=2)=[C:31]([CH3:45])[O:30][N:29]=1>ClCCl>[CH3:27][C:28]1[C:32]([CH2:33][O:34][C:35]2[CH:36]=[CH:37][C:38]([S:41]([NH:8][C:7]3[C:2]([CH3:1])=[N:3][C:4]([CH:9]4[CH2:13][CH2:12][N:11]([CH2:14][C:15]5[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=5)[CH2:10]4)=[CH:5][CH:6]=3)(=[O:43])=[O:42])=[CH:39][CH:40]=2)=[C:31]([CH3:45])[O:30][N:29]=1

참가 물질

5

반응물 3

HCID 1049Pyridine2회HCID 164907024-((3,5-Dimethylisoxazol-4-yl)methoxy)benzene-1-sulfonyl chloride2회HCID 898759382-Methyl-6-[1-(phenylmethyl)-3-pyrrolidinyl]-3-pyridinamine

생성물 1

HCID 898763124-{[(3,5-dimethyl-4-isoxazolyl)methyl]oxy}-N-{2-methyl-6-[1-(phenylmethyl)-3-pyrrolidinyl]-3-pyridinyl}benzenesulfonamide수율 71%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

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온도
65 °C

실험 절차

To a solution of 2-methyl-6-[1-(phenylmethyl)-3-pyrrolidinyl]-3-pyridinamine (150 mg, 0.561 mmol) in dichloromethane (DCM) (4 mL) and pyridine (0.045 mL, 0.561 mmol) was added 4-{[(3,5-dimethyl-4-isoxazolyl)methyl]oxy}benzenesulfonyl chloride (169 mg, 0.561 mmol). The reaction vessel was sealed and heated at 65° C. for 2 hours. Additional 4-{[(3,5-dimethyl-4-isoxazolyl)methyl]oxy}benzenesulfonyl chloride (169 mg, 0.561 mmol) and pyridine (0.045 mL, 0.561 mmol) were added and the reaction mixture was heated for a further 4 hours at 65° C. The reaction mixture was then cooled and separated between DCM (40 mL) and saturated sodium bicarbonate solution (30 mL). The organic phase was passed through a hydrophobic frit and evaporated in vacuo. The sample was purified by flash silica (Si) chromatography (0-25% methanol-dichloromethane gradient). The appropriate fractions were combined and evaporated in vacuo to give the title product (211 mg) as a brown gum (approx 71% pure). LCMS (2 min, formic) Rt 0.80 min, m/z (ES+) 533 (M+H)

후처리

  1. customThe reaction vessel was sealed
  2. temperaturethe reaction mixture was heated for a further 4 hours at 65° C
  3. temperatureThe reaction mixture was then cooled
  4. customseparated between DCM (40 mL) and saturated sodium bicarbonate solution (30 mL)
  5. customevaporated in vacuo
  6. customThe sample was purified by flash silica (Si) chromatography (0-25% methanol-dichloromethane gradient)
  7. customevaporated in vacuo

출처 및 근거

ORD 기록
ord-73b7553424594b3f9019ee61d966bee8
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09242972B2

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