Water → 3-(1-(4-Amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-phenyl-1H-isochromen-1-one

HRID 634406Notes

Reaction equation

HRID 634406 reaction equation
[I: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.Br[CH:13]([C:15]1[O:16][C:17](=[O:31])[C:18]2[C:23]([C:24]=1[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH3:14].C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[NH2:11][C:9]1[N:8]=[CH:7][N:6]=[C:5]2[N:4]([CH:13]([C:15]3[O:16][C:17](=[O:31])[C:18]4[C:23]([C:24]=3[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[CH:22][CH:21]=[CH:20][CH:19]=4)[CH3:14])[N:3]=[C:2]([I:1])[C:10]=12.[NH2:11][C:9]1[C:10]2[C:5](=[N:4][N:3]([CH:13]([C:15]3[O:16][C:17](=[O:31])[C:18]4[C:23]([C:24]=3[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[CH:22][CH:21]=[CH:20][CH:19]=4)[CH3:14])[C:2]=2[I:1])[N:6]=[CH:7][N:8]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 1181310753-(1-Bromoethyl)-4-phenyl-1H-isochromen-1-one2×HCID 178508725HCID 178508725, compound

Product 2

HCID 1181310533-(1-(4-Amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-phenyl-1H-isochromen-1-oneYield 10%HCID 1181313203-(1-(4-amino-3-iodo-2H-pyrazolo[3,4-d]pyrimidin-2-yl)ethyl)-4-phenyl-1H-isochromen-1-oneYield 2.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Commercially available 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (270 mg, 1.033 mmol) and 3-(1-bromoethyl)-4-phenyl-1H-isochromen-1-one (intermediate C7, 500 mg, 1.519 mmol) were dissolved in DMF (4 mL). K2CO3 (315 mg, 2.278 mmol) was added and the resulting mixture was stirred at 80° C. for 1 hr. The mixture was poured into water (50 ml) and extracted with AcOEt (10 ml×3). Organic phases were dried and evaporated under reduced pressure. The crude was purified via reverse phase chromatography with a Biotage C18 SNAP 60 g column (Phase A, water 95%, ACN 4.9%, formic acid 0.1%); Phase B ACN 95%, water 5%, formic acid 0.1%) to give 3-(1-(4-Amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-phenyl-1H-isochromen-1-one (intermediate D2a, 78 mg, 10%) and 3-(1-(4-amino-3-iodo-2H-pyrazolo[3,4-d]pyrimidin-2-yl)ethyl)-4-phenyl-1H-isochromen-1-one (intermediate D2b, 20 mg, 2.6%).

Workup

  1. extractionextracted with AcOEt (10 ml×3)
  2. customOrganic phases were dried
  3. customevaporated under reduced pressure
  4. customThe crude was purified via reverse phase chromatography with a Biotage C18 SNAP 60 g column (Phase A, water 95%, ACN 4.9%, formic acid 0.1%)

Sources & evidence

ORD record
ord-0708f1c73cba42568ef97704ad062188
Source dataset
uspto-grants-2016_04
Patent number
US09321776B2

Reaction notes

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