2,2-dimethyl-2,3-dihydro-1-benzofuran-5-sulfonyl chloride → 2,2-dimethyl-N-(3-methyl-1-(quinolin-5-yl)-1H-pyrazol-5-yl)-2,3-dihydrobenzofuran-5-sulfonamide

HRID 1406556Notes

Reaction equation

HRID 1406556 reaction equation
[CH3:1][C:2]1([CH3:15])[CH2:6][C:5]2[CH:7]=[C:8]([S:11](Cl)(=[O:13])=[O:12])[CH:9]=[CH:10][C:4]=2[O:3]1.[CH3:16][C:17]1[CH:21]=[C:20]([NH2:22])[N:19]([C:23]2[CH:32]=[CH:31][CH:30]=[C:29]3[C:24]=2[CH:25]=[CH:26][CH:27]=[N:28]3)[N:18]=1>N1C=CC=CC=1>[CH3:1][C:2]1([CH3:15])[CH2:6][C:5]2[CH:7]=[C:8]([S:11]([NH:22][C:20]3[N:19]([C:23]4[CH:32]=[CH:31][CH:30]=[C:29]5[C:24]=4[CH:25]=[CH:26][CH:27]=[N:28]5)[N:18]=[C:17]([CH3:16])[CH:21]=3)(=[O:13])=[O:12])[CH:9]=[CH:10][C:4]=2[O:3]1

Participants

4

Reactant 2

HCID 156110382,2-dimethyl-2,3-dihydro-1-benzofuran-5-sulfonyl chlorideHCID 866945143-methyl-1-(quinolin-5-yl)-1H-pyrazol-5-amine

Product 1

HCID 866945212,2-dimethyl-N-(3-methyl-1-(quinolin-5-yl)-1H-pyrazol-5-yl)-2,3-dihydrobenzofuran-5-sulfonamideYield 40%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
80 °C

Procedure

A stirring mixture of 2,2-dimethyl-2,3-dihydro-1-benzofuran-5-sulfonyl chloride (0.10 g, 0.41 mmol) and 3-methyl-1-(quinolin-5-yl)-1H-pyrazol-5-amine (prepared from Example 4 step b, 0.11 g, 0.49 mmol) in pyridine (0.41 mL) was heated at 80° C. for 1 h. After cooling to room temperature, the reaction mixture was concentrated in vacuo. The crude residue was purified by flash chromatography (SiO2, 0-20% ethyl acetate in hexanes), followed by reverse phase HPLC(C18 column, acetonitrile-H2O with 0.1% TFA as eluent) to give the title compound as a white solid (0.070 g, 0.16 mmol, 40%). 1H NMR (400 MHz, CDCl3) δ 8.82 (s, 1H), 8.06 (d, J=8.0 Hz, 1H), 7.60 (t, J=7.6 Hz, 1H), 7.54 (d, J=8.0 Hz, 1H), 7.42 (d, J=8.4 Hz, 1H), 7.31 (s, 1H), 7.24 (d, J=3.2 Hz, 1H), 7.19 (d, J=6.8 Hz, 1H), 6.61 (d, J=8.8 Hz, 1H), 6.24 (s, 1H), 2.89 (s, 2H), 2.34 (s, 3H), 1.51 (s, 6H); MS: (ES) m/z calculated for C23H23N4O3S [M+H]+ 435.2. found 435.3.

Workup

  1. temperatureAfter cooling to room temperature
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. customThe crude residue was purified by flash chromatography (SiO2, 0-20% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-52ef8f291ab042848520874536b31c04
Source dataset
uspto-grants-2014_12
Patent number
US08916601B2

Reaction notes

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