Potassium Fluoride → HCID 16035854, compound

HRID 1987134Notes

Reaction equation

HRID 1987134 reaction equation
Cl[C:2]1[CH:3]=[C:4]2[C:12](=[O:13])[C:11]3[CH:14]=[C:15]([CH:18]([OH:33])[CH2:19][N:20]4[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21]4)[CH:16]=[CH:17][C:10]=3[CH:9]=[CH:8][C:5]2=[N:6][CH:7]=1.[CH3:34][N:35]1[CH:39]=[C:38](B2OC(C)(C)C(C)(C)O2)[CH:37]=[N:36]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]>[OH:33][CH: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:38]4[CH:37]=[N:36][N:35]([CH3:34])[CH:39]=4)[CH:3]=[C:4]3[C:12](=[O:13])[C:11]=2[CH:14]=1)[CH2:19][N:20]1[CH2:21][CH2:22][N:23]([C:26]([O:28][C:29]([CH3:30])([CH3:32])[CH3:31])=[O:27])[CH2:24][CH2:25]1

Participants

5

Reactant 3

HCID 522689Potassium FluorideHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 16035853HCID 16035853, compound

Product 1

HCID 16035854HCID 16035854, compound

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

tert-Butyl 4-[2-(3-chloro-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl)-2-hydroxyethyl]piperazine-1-carboxylate (65 mg, 0.138 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (58 mg, 0.28 mol), Pd2(dba)3 (6 mg, 0.007 mmol), (tBu3)PBF4 (4 mg, 0.014 mmol), and potassium fluoride (27 mg, 0.46 mmol) were combined in a sealed tube which was evacuated and backfilled with argon three times. Fully degassed DMF (1.5 mL) was added. The tube was placed in an oil bath at 115° C. and stirred for 19 hours. The reaction mixture was poured into an ethyl acetate/brine mixture and extracted with ethyl acetate. Combined organics were dried over magnesium sulfate, filtered, concentrated in vacuo, and purified via reverse phase HPLC (10-42% acetonitrile/water gradient, 0.05% trifluoroacetic acid modifier) to afford the title compound. 1H NMR (600 MHz, CDCl3) δ 9.00 (d, 1H); 8.55 (d, 1H); 8.23 (d, 1H); 7.91 (s, 1H); 7.80 (s, 1H); 7.76 (dd, 1H); 7.60 (d, 1H); 7.34 (d, 1H); 7.23 (d, 1H); 4.95 (d, 1H); 3.98 (s, 3H); 3.56-3.51 (m, 4H); 2.78-2.53 (m, 6H); 1.46 (s, 9H). Hydroxyl proton was not observed. LRMS (APCI) calc'd for (C29H34N5O4) [M+H]+, 516.3; found 516.3.

Workup

  1. customwhich was evacuated
  2. additionFully degassed DMF (1.5 mL) was added
  3. customThe tube was placed in an oil bath at 115° C.
  4. additionThe reaction mixture was poured into an ethyl acetate/brine mixture
  5. extractionextracted with ethyl acetate
  6. dry with materialCombined organics were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. custompurified via reverse phase HPLC (10-42% acetonitrile/water gradient, 0.05% trifluoroacetic acid modifier)

Sources & evidence

ORD record
ord-adcf9a57dc4549018a1ad193c3c02a07
Source dataset
uspto-grants-2009_06
Patent number
US07550478B2

Reaction notes

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