Potassium Iodide → 6-{3-[1-(4-Amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-methoxy-6-methylphenyl}morpholin-3-one

HRID 1499946Notes

Reaction equation

HRID 1499946 reaction equation
[Cl:1][C:2]1[C:3]([CH3:20])=[C:4]([CH:13]2[CH2:18][NH:17][C:16](=[O:19])[CH2:15][O:14]2)[C:5]([O:11][CH3:12])=[C:6]([CH:8](Cl)[CH3:9])[CH:7]=1.[CH3:21][C:22]1[C:30]2[C:25](=[N:26][CH:27]=[N:28][C:29]=2[NH2:31])[NH:24][N:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[K+]>CN(C)C=O.CCOCC>[NH2:31][C:29]1[N:28]=[CH:27][N:26]=[C:25]2[N:24]([CH:8]([C:6]3[C:5]([O:11][CH3:12])=[C:4]([CH:13]4[CH2:18][NH:17][C:16](=[O:19])[CH2:15][O:14]4)[C:3]([CH3:20])=[C:2]([Cl:1])[CH:7]=3)[CH3:9])[N:23]=[C:22]([CH3:21])[C:30]=12

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 10796Cesium carbonateHCID 866778616-[3-Chloro-5-(1-chloroethyl)-6-methoxy-2-methylphenyl]morpholin-3-oneHCID 178434474HCID 178434474, compound

Product 1

HCID 866778626-{3-[1-(4-Amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-methoxy-6-methylphenyl}morpholin-3-one

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

A mix of 6-[3-chloro-5-(1-chloroethyl)-6-methoxy-2-methylphenyl]morpholin-3-one (19.0 mg, 0.0597 mmol) (racemic mixture of two diastereomers from step 6) 3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (11 mg, 0.072 mmol), cesium carbonate (29 mg, 0.090 mmol) and potassium iodide (0.99 mg, 0.006 mmol) in N,N-dimethylformamide (0.19 mL) was heated at 140° C. for 1 hour. The mixture was diluted with ether, washed with water, concentrated and purified by preparative LCMS (pH 10) using RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min) to give 2.5 mg, 10% of Peak 1 (single enantiomer, retention time 10.15 min): LCMS calculated for C20H24ClN6O3 (M+H)+: m/z=431.2; found: 431.1, and 2.7 mg, 10% of Peak 2 (single enantiomer, retention time 10.76 min): LCMS calculated for C20H24ClN6O3 (M+H)+: m/z=431.2; found: 431.1.

Workup

  1. washwashed with water
  2. concentrationconcentrated
  3. custompurified by preparative LCMS (pH 10)
  4. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min)
  5. customto give 2.5 mg, 10% of Peak 1 (single enantiomer, retention time 10.15 min)

Sources & evidence

ORD record
ord-66129b11c5a14e3db35d534731fa4494
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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