Potassium Phosphate, Tribasic → HCID 86679695, compound

HRID 1507116Notes

Reaction equation

HRID 1507116 reaction equation
I[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[N:6]=[C:5]2[CH:17]=[O:18].B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.CC([O-])=O.[K+].[O-]P([O-])([O-])=O.[K+].[K+].[K+].Br[C:51]1[CH:52]=[C:53]([NH:57][C:58](=[O:62])[N:59]([CH3:61])[CH3:60])[CH:54]=[N:55][CH:56]=1>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].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.CN(C=O)C>[CH:17]([C:5]1[C:4]2[C:8](=[CH:9][CH:10]=[C:2]([C:51]3[CH:52]=[C:53]([NH:57][C:58](=[O:62])[N:59]([CH3:60])[CH3:61])[CH:54]=[N:55][CH:56]=3)[CH:3]=2)[N:7]([CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)[N:6]=1)=[O:18]

Participants

10

Reactant 5

HCID 62657Potassium Phosphate, TribasicHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 205807365-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carbaldehydeHCID 86679690HCID 86679690, compound

Product 1

HCID 86679695HCID 86679695, compoundYield 18%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 5-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carbaldehyde (CXIV) (1.780 g, 5.0 mmol), bis(pinacolato)diboron (1.523 g, 6.0 mmol), KOAc (1.471 g, 15 mmol) and dry DMF (20 mL) was purged with argon. PdCl2(dppf)2 (0.245 g, 0.3 mmol) was added to the reaction and purged again with argon. The solution was heated at 90° C. for 2 h. Once TLC showed the disappearance of (CXIV), the solution was cooled to room temperature. To this solution was added K3PO4 (1.592 g, 7.5 mmol), 3-(5-bromopyridin-3-yl)-1,1-dimethylurea (XXII) (1.220 g, 5.0 mmol), Pd(PPh3)4 (173 mg, 0.15 mmol) and water (2 mL). The solution was purged with argon and heated at 90° C. for 3 h. The solution was cooled to room temperature and then concentrated under reduced pressure. The residue was dissolved in DCM and washed with water, dried over MgSO4, filtered and then evaporated under vacuum. The residue was purified on a silica gel column (100% DCM→2:98 MeOH:DCM) to give 3-(5-(3-formyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-1,1-dimethylurea (CXXIII) as a brown viscous oil which solidified under vacuum at room temperature (354 mg, 0.90 mmol, 18% yield for 2 steps). 1H NMR (DMSO-d6) δ ppm 10.22 (s, 1H), 8.76 (d, J=1.6 Hz, 1H), 8.63 (s, 1H), 8.52 (d, J=1.6 Hz, 1H), 8.36 (s, 1H), 8.24 (m, 1H), 8.05 (d, J=7.2 Hz, 1H), 7.91 (dd, J=7.2, 1.4 Hz, 1H), 6.13 (dd, J=7.6, 2.0 Hz, 1H), 3.93 (m, 1H), 3.85 (m, 1H), 2.98 (s, 6H), 2.47-2.42 (m, 1H), 2.11-2.06 (m, 2H), 1.82-1.79 (m, 1H) 1.64 (m, 2H); ESIMS found for C21H23N5O3 m/z 394.0 (M+H).

Workup

  1. custompurged again with argon
  2. temperaturethe solution was cooled to room temperature
  3. customThe solution was purged with argon
  4. temperatureheated at 90° C. for 3 h
  5. temperatureThe solution was cooled to room temperature
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe residue was dissolved in DCM
  8. washwashed with water
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. customevaporated under vacuum
  12. customThe residue was purified on a silica gel column (100% DCM→2:98 MeOH:DCM)

Sources & evidence

ORD record
ord-2687e5d4c52e44dd9a12accaa04e729f
Source dataset
uspto-grants-2015_12
Patent number
US09221793B2

Reaction notes

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