Pyrrolidine → HCID 178489376, compound

HRID 272043Notes

Reaction equation

HRID 272043 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-ec6e6b0c8f764688a779c8c608c592e8
Source dataset
uspto-grants-2008_11
Patent number
US07452993B2

Reaction notes

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