Toluene → HCID 22136266, compound

HRID 2113795Notes

Reaction equation

HRID 2113795 reaction equation
[CH3:1][N:2]1[C:10]([NH2:11])=[C:9]2[C:4]([N:5]([C:12]3[C:17]([CH3:18])=[CH:16][C:15]([CH3:19])=[CH:14][C:13]=3[CH3:20])[CH2:6][CH2:7][CH2:8]2)=[N:3]1.CCN(CC)CC.[CH3:28][O:29][CH2:30][C:31](=O)[CH2:32][CH3:33].C1(C)C=CC=CC=1.[BH3-]C#N.[Na+]>C(Cl)Cl.CO.Cl[Ti](Cl)(Cl)Cl>[CH3:28][O:29][CH2:30][CH:31]([NH:11][C:10]1[N:2]([CH3:1])[N:3]=[C:4]2[C:9]=1[CH2:8][CH2:7][CH2:6][N:5]2[C:12]1[C:17]([CH3:18])=[CH:16][C:15]([CH3:19])=[CH:14][C:13]=1[CH3:20])[CH2:32][CH3:33]

Participants

9

Reactant 5

HCID 1140TolueneHCID 8471TriethylamineHCID 5003444Sodium cyanoborohydrideHCID 100803451-methoxybutan-2-oneHCID 22136293HCID 22136293, compound

Product 1

HCID 22136266HCID 22136266, compoundYield 77%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

2-Methyl-7-(2,4,6-trimethyl-phenyl)-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridin-3-ylamine (5-44; 101 mg, 0.373 mmol) was dissolved in CH2Cl2 (2 mL). Et3N (0.25 mL, 1.79 mmol) and the 1-methoxy-butan-2-one (65 mg, 0.636 mmol) were added at room temperature. A solution of TiCl4 in toluene (1 M; 0.35 mL, 0.35 mmol) was added dropwise via syringe. The mixture was then stirred at room temperature overnight. NaCNBH3 (120 mg, 1.9 mmol) in methanol (1 mL) was added slowly. The stirring continued at room temperature for 0.5 h and the reaction was quenched by the addition of 2 N NaOH (2 mL). EtOAc was added and the layers were separated. The organic layer was washed with water, brine and dried over MgSO4. The solvent was removed and the residue purified by chromatography on SiO2 (gradient elution: 2% MeOH in CH2Cl2 containing 0.1% NH4OH to 3% MeOH in CH2Cl2 containing 0.15% NH4OH over 20 minutes) to yield 102 mg of 5-40 (0.286 mmol; 77%).

Workup

  1. waitThe stirring continued at room temperature for 0.5 h
  2. customthe reaction was quenched by the addition of 2 N NaOH (2 mL)
  3. additionEtOAc was added
  4. customthe layers were separated
  5. washThe organic layer was washed with water, brine
  6. dry with materialdried over MgSO4
  7. customThe solvent was removed
  8. customthe residue purified by chromatography on SiO2 (gradient elution: 2% MeOH in CH2Cl2 containing 0.1% NH4OH to 3% MeOH in CH2Cl2 containing 0.15% NH4OH over 20 minutes)

Sources & evidence

ORD record
ord-6ff4fc702df94e76a191377107afc416
Source dataset
uspto-grants-2008_10
Patent number
US07432283B2

Reaction notes

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