1-Bromo-2-methylpropane → N-(6-(1-benzylpyrrolidin-3-yl)-2-methylpyridin-3-yl)-4-((3,5-dimethylisoxazol-4-yl)methoxy)-N-isobutylbenzenesulfonamide

HRID 594136Notes

Reaction equation

HRID 594136 reaction equation
[CH3:1][C:2]1[C:6]([CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([S:15]([NH:18][C:19]3[C:20]([CH3:37])=[N:21][C:22]([CH:25]4[CH2:29][CH2:28][N:27]([CH2:30][C:31]5[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=5)[CH2:26]4)=[CH:23][CH:24]=3)(=[O:17])=[O:16])=[CH:11][CH:10]=2)=[C:5]([CH3:38])[O:4][N:3]=1.[CH3:39][C:40](N=C(N(C)C)N(C)C)([CH3:42])[CH3:41].BrCC(C)C>C(#N)C>[CH2:30]([N:27]1[CH2:28][CH2:29][CH:25]([C:22]2[N:21]=[C:20]([CH3:37])[C:19]([N:18]([CH2:39][CH:40]([CH3:42])[CH3:41])[S:15]([C:12]3[CH:11]=[CH:10][C:9]([O:8][CH2:7][C:6]4[C:2]([CH3:1])=[N:3][O:4][C:5]=4[CH3:38])=[CH:14][CH:13]=3)(=[O:16])=[O:17])=[CH:24][CH:23]=2)[CH2:26]1)[C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1

Participants

5

Reactant 3

HCID 65551-Bromo-2-methylpropaneHCID 35715812-tert-Butyl-1,1,3,3-tetramethylguanidineHCID 898763124-{[(3,5-dimethyl-4-isoxazolyl)methyl]oxy}-N-{2-methyl-6-[1-(phenylmethyl)-3-pyrrolidinyl]-3-pyridinyl}benzenesulfonamide

Product 1

HCID 117925766N-(6-(1-benzylpyrrolidin-3-yl)-2-methylpyridin-3-yl)-4-((3,5-dimethylisoxazol-4-yl)methoxy)-N-isobutylbenzenesulfonamideYield 48.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 4-{[(3,5-dimethyl-4-isoxazolyl)methyl]oxy}-N-{2-methyl-6-[1-(phenylmethyl)-3-pyrrolidinyl]-3-pyridinyl}benzenesulfonamide (211 mg, 0.396 mmol) and N″-(1,1-dimethylethyl)-N,N,N′,N′-tetramethylguanidine (67.9 mg, 0.396 mmol) in acetonitrile (3 mL) was added 1-bromo-2-methylpropane (0.086 mL, 0.792 mmol). The reaction vessel was sealed and heated at 80° C. for 8 hours. The reaction mixture was separated between ethyl acetate and saturated sodium bicarbonate solution. The organic phase was washed with brine and dried over magnesium sulphate. The solvent was removed 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 required product (114 mg) as a brown gum. LCMS (2 min, formic) Rt 1.01 min, m/z (ES+) 589 (M+H)

Workup

  1. customThe reaction vessel was sealed
  2. customThe reaction mixture was separated between ethyl acetate and saturated sodium bicarbonate solution
  3. washThe organic phase was washed with brine
  4. dry with materialdried over magnesium sulphate
  5. customThe solvent was removed 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-2eeafdb7b16949bda4cf8ee3cb6aa7f5
Source dataset
uspto-grants-2016_01
Patent number
US09242972B2

Reaction notes

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