Potassium Fluoride → HCID 16035518, compound

HRID 222283Notes

Reaction equation

HRID 222283 reaction equation
Cl[C:2]1[CH:3]=[C:4]2[C:12](=[O:13])[C:11]3[CH:14]=[C:15]([NH:18][S:19]([N:22]([CH3:28])[CH:23]4[CH2:27][CH2:26][O:25][CH2:24]4)(=[O:21])=[O:20])[CH:16]=[CH:17][C:10]=3[CH:9]=[CH:8][C:5]2=[N:6][CH:7]=1.[CH3:29][N:30]1[CH:34]=[C:33](B2OC(C)(C)C(C)(C)O2)[CH:32]=[N:31]1.[F-].[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CN(C=O)C>[CH3:28][N:22]([CH:23]1[CH2:27][CH2:26][O:25][CH2:24]1)[S:19]([NH:18][C:15]1[CH:16]=[CH:17][C:10]2[CH:9]=[CH:8][C:5]3=[N:6][CH:7]=[C:2]([C:33]4[CH:32]=[N:31][N:30]([CH3:29])[CH:34]=4)[CH:3]=[C:4]3[C:12](=[O:13])[C:11]=2[CH:14]=1)(=[O:21])=[O:20]

Participants

6

Reactant 3

HCID 522689Potassium FluorideHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 57722858HCID 57722858, compound

Product 1

HCID 16035518HCID 16035518, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

N′-(3-chloro-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl)-N-methyl-N-(tetrahydrofuran-3-yl)sulfamide Enantiomer B (0.070 g, 0.17 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.069 g, 0.33 mmol), Pd2(dba)3 (0.008 g, 0.0085 mmol), (tBu3)PBF4 (0.005 g, 0.017 mmol) and potassium fluoride (0.032 g, 0.56 mmol) were combined in a dry tube. 1.0 mL dry DMF was added and argon was bubbled through the solution for five minutes. The tube was sealed and heated in a Biotage Initiator series microwave reactor to 100° C. for 30 minutes. The solution was diluted with ethyl acetate and washed with saturated sodium bicarbonate. The organic layer was dried with magnesium sulfate, filtered, concentrated in vacuo, and purified by HPLC chromatography (20-100% acetonitrile/water gradient, 0.05% trifluoroacetic acid modifier) to afford the crude compound. The crude material was purified by silica chromatography (0-100% ethyl acetate/hexanes gradient, followed by 0-20% methanol/dichloromethane gradient). The isolated material was dissolved in minimal 25% methano/dichloromethane and hexanes were added until precipitation occurred. Precipitate was filtered to afford title compound. 1H NMR (600 MHz, D6-DMSO) □ 10.55 (s, 1H); 9.20 (d, 1H); 8.58 (d, 1H); 8.46 (s, 1H); 8.13 (s, 1H); 7.95 (d, 1H); 7.75 (d, 1H); 7.52 (dd, 1H); 7.32 (d, 1H); 7.22 (d, 1H); 4.48-4.53 (m, 1H); 3.88 (s, 3H); 3.74-3.80 (m, 1H); 3.42-3.54 (m, 3H); 2.68 (s, 3H); 1.93-2.00 (m, 1H); 1.65-1.72 (m, 1H). LRMS (APCI) calc'd for (C23H24N5O4S) [M+H]+, 466.2; found, 466.2.

Workup

  1. customargon was bubbled through the solution for five minutes
  2. customThe tube was sealed
  3. additionThe solution was diluted with ethyl acetate
  4. washwashed with saturated sodium bicarbonate
  5. dry with materialThe organic layer was dried with magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. custompurified by HPLC chromatography (20-100% acetonitrile/water gradient, 0.05% trifluoroacetic acid modifier)
  9. customto afford the crude compound
  10. customThe crude material was purified by silica chromatography (0-100% ethyl acetate/hexanes gradient, followed by 0-20% methanol/dichloromethane gradient)
  11. dissolutionThe isolated material was dissolved in minimal 25%
  12. additionwere added until precipitation
  13. filtrationPrecipitate was filtered

Sources & evidence

ORD record
ord-8e8da0fe3c8b48cbae32efd0bf6632d1
Source dataset
uspto-grants-2012_06
Patent number
US08207186B2

Reaction notes

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