Potassium Iodide → N-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]-3-(2-pyrrolidin-1-ylethoxy)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

HRID 550431Notes

Reaction equation

HRID 550431 reaction equation
Cl[CH2:2][CH2:3][O:4][C:5]1[C:13]2[C:8](=[N:9][CH:10]=[N:11][C:12]=2[NH:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=3)=[C:17]([Cl:29])[CH:16]=2)[NH:7][N:6]=1.[NH:30]1[CH2:34][CH2:33][CH2:32][CH2:31]1.[I-].[K+]>CC(N(C)C)=O>[Cl:29][C:17]1[CH:16]=[C:15]([NH:14][C:12]2[N:11]=[CH:10][N:9]=[C:8]3[NH:7][N:6]=[C:5]([O:4][CH2:3][CH2:2][N:30]4[CH2:34][CH2:33][CH2:32][CH2:31]4)[C:13]=23)[CH:20]=[CH:19][C:18]=1[O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=1

Participants

5

Reactant 3

HCID 4875Potassium IodideHCID 31268PyrrolidineHCID 115028913-(2-chloroethoxy)-N-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Product 1

HCID 11561779N-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]-3-(2-pyrrolidin-1-ylethoxy)-1H-pyrazolo[3,4-d]pyrimidin-4-amineYield 51%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
140 °C

Procedure

3-(2-chloroethoxy)-N-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (prepared as described in Example 13/200 mg, 0.43 mmol), pyrrolidine (178 μL, 2.14 mmol) and potassium iodide (0.43 mmol) were mixed in DMA (2 ml). The mixture was heated at 140° C. for 3 minutes in a microwave reactor. The crude mixture was then filtered and purified by preparative HPLC (column beta-basic, Hypercil 51 μm, 21×100 mm) eluting with a mixture of water and acetonitrile containing 2g/l of ammonium carbonate (gradient). After evaporation of the solvents, the remaining solid was triturated in ether, filtered and dried to give the title compound (101 mg, 51%); NMR Spectrum: 1.66 (br s, 4H), 2.54 (br s, 4H), 2.88 (t, 2H), 4.42 (t, 2H), 5.29 (s, 2H), 7.24 (d, 1H), 7.37 (t, 1H), 7.55-7.58 (m, 2H), 7.86-7.90 (m, 2H), 8.29 (s, 1H), 8.60 (br s, 2H); Mass Spectrum: 466 (MH+).

Workup

  1. filtrationThe crude mixture was then filtered
  2. custompurified by preparative HPLC (column beta-basic, Hypercil 51 μm, 21×100 mm)
  3. washeluting with a mixture of water and acetonitrile containing 2g/l of ammonium carbonate (gradient)
  4. customAfter evaporation of the solvents
  5. customthe remaining solid was triturated in ether
  6. filtrationfiltered
  7. customdried

Sources & evidence

ORD record
ord-28928532cbf54dac9fd3bf25af9e23e4
Source dataset
uspto-grants-2011_05
Patent number
US07947676B2

Reaction notes

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