Potassium Iodide → tert-Butyl 3-{3-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-ethoxy-6-fluorophenyl}azetidine-1-carboxylate

HRID 1499804Notes

Reaction equation

HRID 1499804 reaction equation
[CH3:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[NH:4][N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[K+].[Cl:20][C:21]1[C:22]([F:44])=[C:23]([CH:33]2[CH2:36][N:35]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:34]2)[C:24]([O:30][CH2:31][CH3:32])=[C:25]([CH:27](Cl)[CH3:28])[CH:26]=1>CN(C=O)C>[NH2:11][C:9]1[N:8]=[CH:7][N:6]=[C:5]2[N:4]([CH:27]([C:25]3[C:24]([O:30][CH2:31][CH3:32])=[C:23]([CH:33]4[CH2:34][N:35]([C:37]([O:39][C:40]([CH3:42])([CH3:41])[CH3:43])=[O:38])[CH2:36]4)[C:22]([F:44])=[C:21]([Cl:20])[CH:26]=3)[CH3:28])[N:3]=[C:2]([CH3:1])[C:10]=12

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 10796Cesium carbonateHCID 86677726HCID 86677726, compoundHCID 178434474HCID 178434474, compound

Product 1

HCID 86677728tert-Butyl 3-{3-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-ethoxy-6-fluorophenyl}azetidine-1-carboxylateYield 63.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of 3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (1.10 g, 7.37 mmol), cesium carbonate (3.2 g, 10 mmol) and potassium iodide (111 mg, 0.670 mmol) in DMF (20 mL) was added tert-butyl 3-[3-chloro-5-(1-chloroethyl)-6-ethoxy-2-fluorophenyl]azetidine-1-carboxylate (2.63 g, 6.70 mmol) and the mixture was stirred at 90° C. for 3 h. The solvent was removed in vacuo. The residue was diluted with ethyl acetate and water. Aqueous layer was extracted with ethyl acetate twice. The combined organic layers were washed with water, brine, dried over Na2SO4, filtered and concentrated. The residue was purified on silica gel column (eluting with 100% ethyl acetate) to give the desired product as a foam (2.15 g, 63%). LCMS calculated for C24H31ClFN6O3 (M+H)+: m/z=505.2; Found: 505.2.

Workup

  1. customThe solvent was removed in vacuo
  2. additionThe residue was diluted with ethyl acetate and water
  3. extractionAqueous layer was extracted with ethyl acetate twice
  4. washThe combined organic layers were washed with water, brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified on silica gel column (eluting with 100% ethyl acetate)

Sources & evidence

ORD record
ord-c73606a6816b499f94efad4a59f21ac0
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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