Sodium Carbonate → HCID 66604781, compound

HRID 2410810Notes

Reaction equation

HRID 2410810 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:22]([NH2:24])=[O:23])[C:5]2[NH:6][C:7]3[CH:8]=[C:9]([N:15]4[CH2:20][CH2:19][N:18]([CH3:21])[CH2:17][CH2:16]4)[CH:10]=[CH:11][C:12]=3[C:13]=2[N:14]=1.[CH3:25][N:26]1[CH:30]=[C:29](B2OC(C)(C)C(C)(C)O2)[CH:28]=[N:27]1.C([O-])([O-])=O.[Na+].[Na+]>CO.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[NH3:6].[CH3:25][N:26]1[CH:30]=[C:29]([C:2]2[CH:3]=[C:4]([C:22]([NH2:24])=[O:23])[C:5]3[NH:6][C:7]4[CH:8]=[C:9]([N:15]5[CH2:16][CH2:17][N:18]([CH3:21])[CH2:19][CH2:20]5)[CH:10]=[CH:11][C:12]=4[C:13]=3[N:14]=2)[CH:28]=[N:27]1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 86663052HCID 86663052, compound

Product 2

HCID 222AmmoniaHCID 66604781HCID 66604781, compoundYield 101.5%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

A microwave vial containing a mixture of 2-bromo-7-(4-methylpiperazin-1-yl)-5H-pyrido[3,2-b]indole-4-carboxamide (50 mg, 0.13 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (54 mg, 0.26 mmol), PdCl2(dppf)-CH2Cl2 adduct (11 mg, 0.013 mmol), and 2 N aq. Na2CO3 (0.32 mL, 0.64 mmol) was flushed with nitrogen. DME (5 mL) was added and the vial was sealed and heated at 100 ° C. in an oil bath for 2 hrs. The reaction was diluted with MeOH, filtered, and the solid was washed with MeOH. The solvents were removed from the combined filtrates and preparative HPLC (PHENOMENEX® Luna C18 30×100 10u Column, Solvent A=10 mM NH4OAc in 95% water:5% acetonitrile; B=10 mM NH4OAc in 5% water:95% acetonitrile; 30 to 100% B over 20 min at 30 mL/min. SCX capture and release with 2 N NH3 in MeOH gave 2-(1-methyl-1H-pyrazol-4-yl)-7-(4-methylpiperazin-1-yl)-5H-pyrido[3,2-b]indole-4-carboxamide (27 mg, 0.066 mmol, 51% yield) as a yellow solid. MS (ESI) m/z 401.27 (M+H). 1H NMR (500 MHz, acetone) d ppm 10.66 (1H, br. s.), 9.34 (1H, d, J=1.83 Hz), 8.50 (1H, dd, J=8.09, 2.29 Hz), 8.32 (1H, s), 8.16 (1H, d, J=8.85 Hz), 8.11 (1H, br. s.), 7.36 (1H, d, J=8.24 Hz), 7.30 (1H, d, J=1.83 Hz), 7.12 (1H, br. s.), 7.08 (1H, dd, J=8.70, 2.29 Hz), 3.33-3.40 (4H, m), 2.78 (4H, br. s.), 2.57 (3H, s), 2.31 (3H, s).

Workup

  1. additionA microwave vial containing
  2. customwas flushed with nitrogen
  3. additionDME (5 mL) was added
  4. customthe vial was sealed
  5. additionThe reaction was diluted with MeOH
  6. filtrationfiltered
  7. washthe solid was washed with MeOH
  8. customThe solvents were removed from the combined filtrates and preparative HPLC (PHENOMENEX® Luna C18 30×100 10u Column, Solvent A=10 mM NH4OAc in 95% water

Sources & evidence

ORD record
ord-fbbcb9539b714733ad751245766eb036
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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