Cyclopropylboronic acid → 2-cyclopropyl-7-iodo-2H-pyrazolo[4,3-b]pyridine

HRID 1522567Notes

Reaction equation

HRID 1522567 reaction equation
[Na]N([Si](C)(C)C)[Si](C)(C)C.[I:11][C:12]1[C:13]2[C:14](=[CH:18][NH:19][N:20]=2)[N:15]=[CH:16][CH:17]=1.[CH:21]1(B(O)O)[CH2:23][CH2:22]1>CN(C)C1C=CN=CC=1.C1(C)C=CC=CC=1.C(O[Cu]OC(=O)C)(=O)C>[CH:21]1([N:19]2[CH:18]=[C:14]3[N:15]=[CH:16][CH:17]=[C:12]([I:11])[C:13]3=[N:20]2)[CH2:23][CH2:22]1

Participants

7

Reactant 3

HCID 2760897Cyclopropylboronic acidHCID 178504303sodium bis(trimethylsilyl)azanideHCID 178506553HCID 178506553, compound

Product 1

HCID 674696502-cyclopropyl-7-iodo-2H-pyrazolo[4,3-b]pyridine

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 178476681HCID 178476681, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
95 °C

Procedure

N-Sodiohexamethyldisilazane (3.40 mL, 2.041 mmol), N,N-dimethylpyridin-4-amine (748 mg, 6.12 mmol), 7-iodo-2H-pyrazolo[4,3-b]pyridine (500 mg, 2.041 mmol), diacetoxycopper (371 mg, 2.041 mmol) and cyclopropylboronic acid (351 mg, 4.08 mmol) were combined in toluene (15 mL) and sparged with air. The mixture was heated at 95° C. overnight. The mixture was then cooled and poured into saturated NH4Cl and extracted with EtOAc (2×). The combined organic layers were dried over Na2SO4 and concentrated to give a residue which was purified on silica column chromatography eluted with EtOAc/Hexanes (0-97%) using a step gradient and then to 98% EtOAc to give 2-cyclopropyl-7-iodo-2H-pyrazolo[4,3-b]pyridine. The other fractions were further purified on a second silica column chromatography eluted with EtOAc/Hexanes (0-50%) using a step gradient and then to 90% EtOAc to give the title compounds. MS [M+H] found 286.1.

Workup

  1. customsparged with air
  2. temperatureThe mixture was then cooled
  3. additionpoured into saturated NH4Cl
  4. extractionextracted with EtOAc (2×)
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. concentrationconcentrated
  7. customto give a residue which
  8. customwas purified on silica column chromatography
  9. washeluted with EtOAc/Hexanes (0-97%)

Sources & evidence

ORD record
ord-bdbd53b53c6648a0b73e048fb3823314
Source dataset
uspto-grants-2015_07
Patent number
US09073918B2

Reaction notes

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