Sodium Carbonate → 5-[4-(2-Methylsulfanyl-pyrimidin-4-yl)-1-(tetrahydro-pyran-2-yl)-1H-pyrazol-3-yl]-1H-pyrrolo[2,3-b]pyridine

HRID 500738Notes

Reaction equation

HRID 500738 reaction equation
I[C:2]1[C:6]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([S:13][CH3:14])[N:8]=2)=[CH:5][N:4]([CH:15]2[CH2:20][CH2:19][CH2:18][CH2:17][O:16]2)[N:3]=1.CC1(C)C(C)(C)OB([C:29]2[CH:30]=[C:31]3[CH:37]=[CH:36][NH:35][C:32]3=[N:33][CH:34]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C>[CH3:14][S:13][C:9]1[N:8]=[C:7]([C:6]2[C:2]([C:29]3[CH:30]=[C:31]4[CH:37]=[CH:36][NH:35][C:32]4=[N:33][CH:34]=3)=[N:3][N:4]([CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][O:16]3)[CH:5]=2)[CH:12]=[CH:11][N:10]=1

Participants

5

Reactant 3

HCID 10340Sodium Carbonate2×HCID 242087895-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo(2,3-b)pyridineHCID 594244104-(3-Iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-2-(methylthio)pyrimidine

Product 1

HCID 578562535-[4-(2-Methylsulfanyl-pyrimidin-4-yl)-1-(tetrahydro-pyran-2-yl)-1H-pyrazol-3-yl]-1H-pyrrolo[2,3-b]pyridineYield 69%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of 4-[3-Iodo-1-(tetrahydro-pyran-2-yl)-1H-pyrazol-4-yl]-2-methylsulfanyl-pyrimidine B (1.33 g, 3.3 mmol) and 5-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (1 g, 4.1 mmol) in DMF (30 mL) was added a 2M solution of sodium carbonate (2 mL). The sodium carbonate appeared to come out of solution upon addition. The mixture was deoxygenated with a nitrogen bubbler for a few minutes. The palladium catalyst was added and nitrogen bubbling continued for a few minutes before the bubbler was removed. The mixture was heated at 85° C. for 18 hr. LCMS shows complete conversion to product. The mixture was dropped into saturated aqueous NaCl and the resulting solids collected by filtration and rinsed with water. The solids were dissolved in methanol/dichloromethane (1:9), dried over MgSO4 and reduced to minimum volume. The residue was purified on a short column of silica gel using a gradient of 0-50% ethyl acetate in dichloromethane as eluant to give 5-[4-(2-Methylsulfanyl-pyrimidin-4-yl)-1-(tetrahydro-pyran-2-yl)-1H-pyrazol-3-yl]-1H-pyrrolo[2,3-b]pyridine (C-1-1) (0.89 g, 69%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.73 (br. s., 1H), 8.69 (s, 1H), 8.43 (d, J=5.31 Hz, 1H), 8.29 (d, J=2.02 Hz, 1H), 8.07 (d, J=2.02 Hz, 1H), 7.51 (t, J=3.03 Hz, 1H), 7.11 (d, J=5.31 Hz, 1H), 6.48 (dd, J=3.28, 1.77 Hz, 1H), 5.53 (dd, J=9.85, 2.27 Hz, 1H), 4.00 (br. d, J=13.39 Hz, 1H), 3.61-3.76 (br. m, 1H), 2.10-2.24 (br. m, 4H), 1.91-2.06 (br. m, 2H), 1.65-1.80 (br. m, 1H), 1.50-1.63 (br. m, 2H).

Workup

  1. additionto come out of solution upon addition
  2. customThe mixture was deoxygenated with a nitrogen bubbler for a few minutes
  3. additionThe palladium catalyst was added
  4. waitnitrogen bubbling continued for a few minutes before the bubbler
  5. customwas removed
  6. additionThe mixture was dropped into saturated aqueous NaCl
  7. filtrationthe resulting solids collected by filtration
  8. washrinsed with water
  9. dissolutionThe solids were dissolved in methanol/dichloromethane (1:9)
  10. dry with materialdried over MgSO4
  11. customThe residue was purified on a short column of silica gel using a gradient of 0-50% ethyl acetate in dichloromethane as eluant

Sources & evidence

ORD record
ord-2e1d19e9b8e145689de26a3bba3ca2dd
Source dataset
uspto-grants-2010_08
Patent number
US07772246B2

Reaction notes

Loading…