Nitrogen → 6-chloro-3-cyclopropyl-1-trityl-1H-pyrazolo[4,3-c]pyridine

HRID 571403Notes

Reaction equation

HRID 571403 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]2[C:8](I)=[N:9][N:10]([C:11]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:4]=2[CH:3]=1.[CH:31]1(B(O)O)[CH2:33][CH2:32]1.C(=O)([O-])[O-].[K+].[K+].N#N>O.O1CCOCC1>[Cl:1][C:2]1[N:7]=[CH:6][C:5]2[C:8]([CH:31]3[CH2:33][CH2:32]3)=[N:9][N:10]([C:11]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:4]=2[CH:3]=1

Participants

7

Reactant 4

HCID 947NitrogenHCID 11430Potassium Carbonate2×HCID 2760897Cyclopropylboronic acid2×HCID 895258586-Chloro-3-iodo-1-trityl-1H-pyrazolo[4,3-c]pyridine

Product 1

HCID 1176008606-chloro-3-cyclopropyl-1-trityl-1H-pyrazolo[4,3-c]pyridineYield 84%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

To a flask were added 6-chloro-3-iodo-1-trityl-1H-pyrazolo[4,3-c]pyridine (3a, 2 g, 3.83 mmol), cyclopropylboronic acid (0.560 g, 6.52 mmol)), potassium carbonate (1.3 g, 9.6 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(ii) dichloride dichloromethane complex (0.157 g, 0.192 mmol), dioxane (10 ml), and water (5 ml). The mixture was Vac/N2 purged 6 times and heated at 60° C. After 5 h, the reaction was treated further with cyclopropylboronic acid (0.560 g, 6.52 mmol)), potassium carbonate (1.3 g, 9.6 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(ii)dichloride dichloromethane complex (0.157 g, 0.192 mmol), then degassed, and then heated at 80° C. overnight. The mixture was diluted with DCM and water and then filtered through celite. The organic phase was separated and concentrated to afford a dark residue, which was purified on silica gel (40 g, 0-20% ethyl acetate/hexanes) to afford 6-chloro-3-cyclopropyl-1-trityl-1H-pyrazolo[4,3-c]pyridine (1.4 g, 84% yield) as a white foam. MS ESI calc'd. for C28H22Cl1N3[M+1]+ 436, found 436.

Workup

  1. custompurged 6 times
  2. customdegassed
  3. temperatureheated at 80° C. overnight
  4. additionThe mixture was diluted with DCM and water
  5. filtrationfiltered through celite
  6. customThe organic phase was separated
  7. concentrationconcentrated
  8. customto afford a dark residue, which
  9. customwas purified on silica gel (40 g, 0-20% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-58d3158d917841b9ae361629cda17768
Source dataset
uspto-grants-2015_05
Patent number
US09023865B2

Reaction notes

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