Potassium Carbonate → HCID 53380866, compound

HRID 515217Notes

Reaction equation

HRID 515217 reaction equation
[F:1][C:2]1([F:27])[CH2:4][CH:3]1[CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][C:13]([C:15]3[CH:22]=[C:21]([OH:23])[CH:20]=[CH:19][C:16]=3[C:17]#[N:18])=[CH:14][C:9]=2[N:8]([CH3:24])[S:7]1(=[O:26])=[O:25].Cl[C:29]1[N:34]=[C:33]([C:35]#[N:36])[CH:32]=[CH:31][CH:30]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[C:17]([C:16]1[CH:19]=[CH:20][C:21]([O:23][C:29]2[N:34]=[C:33]([C:35]#[N:36])[CH:32]=[CH:31][CH:30]=2)=[CH:22][C:15]=1[C:13]1[CH:12]=[CH:11][C:10]2[N:6]([CH2:5][CH:3]3[CH2:4][C:2]3([F:1])[F:27])[S:7](=[O:26])(=[O:25])[N:8]([CH3:24])[C:9]=2[CH:14]=1)#[N:18]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 1184246-Chloropyridine-2-carbonitrileHCID 67409967HCID 67409967, compound

Product 1

HCID 53380866HCID 53380866, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
140 °C

Procedure

2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-4-hydroxybenzonitrile (12-2) (300 mg, 0.77 mmol, 1 eq) was dissolved in acetonitrile (2.5 mL) and 6-chloropyridine-2-carbonitrile (212 mg, 1.5 mmol, 2 eq) and potassium carbonate (424 mg, 3.1 mmol, 4 eq) were added. The resulting mixture was heated in the microwave at 140° C. for 1.5 hours. The mixture was filtered washing with acetonitrile. The crude mixture was purified by reverse phase chromatography (Waters Sunfire MSC18, 10-100% acetonitrile in water with 0.1% TFA modifier) to afford 6-(4-cyano-3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}phenoxy)pyridine-2-carbonitrile (12-3) as an off-white solid. 1H NMR (400 MHz, CDCl3): δ 7.90 (t, J=8.0 Hz, 1 H); 7.82 (d, J=8.4 Hz, 1 H); 7.50 (d, J=7.2 Hz, 1H); 7.34 (s, 1H); 7.29 (t, J=10.4 Hz, 1 H); 6.99 (s, 2 H); 6.92 (d, J=8.0 Hz, 2H), 3.92 (d, J=6.8 Hz, 2H); 3.36 (s, 3 H); 2.14 (m, 1 H); 1.65 (m, 1 H); 1.41 (m, 1 H). HRMS m/z (M+H) 494.1097 found, 494.1093 required.

Workup

  1. filtrationThe mixture was filtered
  2. washwashing with acetonitrile
  3. customThe crude mixture was purified by reverse phase chromatography (Waters Sunfire MSC18, 10-100% acetonitrile in water with 0.1% TFA modifier)

Sources & evidence

ORD record
ord-68f9825ba8a84717abbcb60fea444b29
Source dataset
uspto-grants-2015_08
Patent number
US09108937B2

Reaction notes

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