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

HRID 594135Notes

Reaction equation

HRID 594135 reaction equation
[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

Participants

5

Reactant 3

HCID 1049Pyridine2×HCID 164907024-((3,5-Dimethylisoxazol-4-yl)methoxy)benzene-1-sulfonyl chloride2×HCID 898759382-Methyl-6-[1-(phenylmethyl)-3-pyrrolidinyl]-3-pyridinamine

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
65 °C

Procedure

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)

Workup

  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

Sources & evidence

ORD record
ord-73b7553424594b3f9019ee61d966bee8
Source dataset
uspto-grants-2016_01
Patent number
US09242972B2

Reaction notes

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