1,10-Phenanthroline → 4-[7-(2-Chloro-4,6-dimethylphenyl)-2-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridin-3-yl]heptan-4-ol

HRID 1826953Notes

Reaction equation

HRID 1826953 reaction equation
Br[C:2]1[N:3]([CH3:20])[N:4]=[C:5]2[C:10]=1[CH2:9][CH2:8][CH2:7][N:6]2[C:11]1[C:16]([CH3:17])=[CH:15][C:14]([CH3:18])=[CH:13][C:12]=1[Cl:19].N1C2C(=CC=C3C=2N=CC=C3)C=CC=1.C([Li])CCC.[CH3:40][CH2:41][CH2:42][C:43](=[O:47])[CH2:44][CH2:45][CH3:46]>O1CCCC1.C1CCCCC1>[Cl:19][C:12]1[CH:13]=[C:14]([CH3:18])[CH:15]=[C:16]([CH3:17])[C:11]=1[N:6]1[CH2:7][CH2:8][CH2:9][C:10]2=[C:2]([C:43]([OH:47])([CH2:44][CH2:45][CH3:46])[CH2:42][CH2:41][CH3:40])[N:3]([CH3:20])[N:4]=[C:5]12

Participants

7

Reactant 4

HCID 13181,10-PhenanthrolineHCID 312464-HeptanoneHCID 113602163-bromo-7-(2-chloro-4,6-dimethylphenyl)-2-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridineHCID 178418339Butyllithium

Product 1

HCID 101728344-[7-(2-Chloro-4,6-dimethylphenyl)-2-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridin-3-yl]heptan-4-olYield 56.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8078CyclohexaneSolvent

Conditions

Temperature
-78 °C

Procedure

3-Bromo-7-(2-chloro-4,6-dimethylphenyl)-2-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridine (122 mg) and a crystal of 1,10-phenanthroline were dissolved in 3 mL of dry tetrahydrofuran and the solution was chilled to −78° C. under an atmosphere of argon. Then nbutyllithium (2.0 M in cyclohexane) was added until the dark color of the organolithium/phenanthroline complex persisted. An additional 0.17 mL of the butyllithium solution then was added. After 10 min, a solution of 4-heptanone (42.6 mg) in 1 mL tetrahydrofuran was added via syringe. The reaction mixture was allowed to stir at −78° C. for 15 min, then was allowed to warm to 0° C. After quenching with aqueous ammonium chloride, the reaction mixture was partitioned between ethyl acetate and brine. The ethyl acetate was dried with magnesium sulfate and concentrated on the rotary evaporator. The residue was chromatographed on silica gel eluting with 9:1 hexane/acetone to provide 76.0 mg of 4-[7-(2-chloro-4,6-dimethylphenyl)-2-methyl-4,5,6,7-tetrahydro-2H-pyrazolo-[3,4-b]pyridin-3-yl]heptan-4-ol, which was recrystallized from hexane, mp 129–130 ° C.

Workup

  1. temperatureto warm to 0° C
  2. customAfter quenching with aqueous ammonium chloride
  3. customthe reaction mixture was partitioned between ethyl acetate and brine
  4. dry with materialThe ethyl acetate was dried with magnesium sulfate
  5. concentrationconcentrated on the rotary evaporator
  6. customThe residue was chromatographed on silica gel eluting with 9:1 hexane/acetone

Sources & evidence

ORD record
ord-085e4d22505f4442916eccb2b2861b51
Source dataset
uspto-grants-2006_05
Patent number
US07053103B2

Reaction notes

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