Pyrrolidine → HCID 178489376, compound

HRID 2388951Notes

Reaction equation

HRID 2388951 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:18]3[CH:19]=[C:20]([CH:23]=[CH:24][CH:25]=3)[CH:21]=O)[CH:16]=2)[N:11](COCC[Si](C)(C)C)[N:10]=1.[NH:34]1[CH2:38][CH2:37][CH2:36][CH2:35]1.Cl([O-])(=O)(=O)=O>C(O)(=O)C>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:18]3[CH:25]=[CH:24][CH:23]=[C:20]([CH2:21][N:34]4[CH2:38][CH2:37][CH2:36][CH2:35]4)[CH:19]=3)[CH:16]=2)[NH:11][N:10]=1

Participants

5

Reactant 3

HCID 31268PyrrolidineHCID 123351PerchlorateHCID 59836136HCID 59836136, compound

Product 1

HCID 178489376HCID 178489376, compoundYield 44.2%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent2×

Procedure

To a solution of 3-[3-(2-Methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-benzaldehyde (23 mg, 0.050 mmol) and Pyrrolidine (5 ul, 0.082 mmol) in 1.5 ml dichloethane was added 3 ul of AcOH. The mixture was stirred at room temperature for 30 mins, and then to the mixture was added sodium trioxyacetylborohydride (22 mg, 0.10 mmol) in one portion. The reaction was continued at room temperature for another 2 hrs the mixture was then concentrated to yield the SEM product which was treated with a solution of 5% perchlorate in acetic acid (2 mL) at room temperature for 1 hr. Solvents were evaporated, the residue was neutralized with sodium bicarbonate powder and then purified by flash silica gel chromatography using ethyl acetate then a mixture of EtOAc/DCM/MeOH/NH4OH (4/4/1/0.05) to afford 3-(2-Methoxy-phenyl)-5-(3-pyrrolidin-1-ylmethyl-phenyl)-1H-pyrazolo[3,4-b]pyridine (8.50 mg, 44% yield) as a white solid. 1H NMR (500 MHz, CD3OD) δ 1.89 (d, J=3 Hz, 4H), 2.76 (d, J=1.5 Hz, 4H), 3.89 (s, 2H), 3.9 (s, 2H), 7.11 (t, J=1 Hz, 1H), 7.22 (d, J=8 Hz, 1H), 7.42 (t, J=7 Hz, 1H), 7.47 (d, J=1.5 Hz, 1H), 7.48 (d, J=2 Hz, 1H), 7.51 (d, J=2.5 Hz, 1H), 7.65 (t, J=6.75 Hz, 1H), 7.72 (s, 1H), 8.39 (d, J=2.5 Hz, 1H), 8.83 (d, J=2 Hz, 1H). MS: m/z 385 [MH+].

Workup

  1. waitThe reaction was continued at room temperature for another 2 hrs
  2. concentrationthe mixture was then concentrated
  3. customto yield the SEM product which
  4. customSolvents were evaporated
  5. custompurified by flash silica gel chromatography
  6. additiona mixture of EtOAc/DCM/MeOH/NH4OH (4/4/1/0.05)

Sources & evidence

ORD record
ord-cff56087732e4889971cd4f372b437ce
Source dataset
uspto-grants-2012_09
Patent number
US08268994B2

Reaction notes

Loading…