Sodium Carbonate → HCID 58158259, compound

HRID 2368823Notes

Reaction equation

HRID 2368823 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:12][C:13]3[N:14]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=4[CH3:30])[C:15](=[O:23])[C:16]4[C:21]([CH3:22])=[CH:20][S:19][C:17]=4[N:18]=3)[N:9]=[C:10](I)[C:3]=12.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[F:50][C:51]1[CH:52]=[C:53](B(O)O)[CH:54]=[C:55]([OH:57])[CH:56]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.C(O)C.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:12][C:13]3[N:14]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=4[CH3:30])[C:15](=[O:23])[C:16]4[C:21]([CH3:22])=[CH:20][S:19][C:17]=4[N:18]=3)[N:9]=[C:10]([C:53]3[CH:52]=[CH:51][CH:56]=[C:55]([OH:57])[CH:54]=3)[C:3]=12.[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:12][C:13]3[N:14]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=4[CH3:30])[C:15](=[O:23])[C:16]4[C:21]([CH3:22])=[CH:20][S:19][C:17]=4[N:18]=3)[N:9]=[C:10]([C:53]3[CH:54]=[C:55]([OH:57])[CH:56]=[C:51]([F:50])[CH:52]=3)[C:3]=12

Participants

10

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 447173083-Fluoro-5-hydroxybenzeneboronic acidHCID 58158239HCID 58158239, compound

Product 2

HCID 58158199HCID 58158199, compoundHCID 58158259HCID 58158259, compoundYield 96.5%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

2-((4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-5-methyl-3-o-tolylthieno[2,3-d]pyrimidin-4(3H)-one (2406) (50 mg, 0.092 mmol), PPh3 (14.5 mg, 0.056 mmol, 0.6 eq) and 3-fluoro-5-hydroxyphenylboronic acid (2207) (17.2 mg, 0.11 mmol, 1.2 eq) were dissolved in a solution of DMF, ethanol and water (5 mL/2 mL/2 mL). To this mixture Pd(OAc)2 (4.14 mg, 0.018 mmol, 0.2 eq) and sodium carbonate (48.7 mg, 0.46 mmol, 5 eq) were added sequentially. The resulting mixture was degassed and back-filled with argon three times and then heated to 80° C. for 0.5 h with stirring. The reaction mixture was concentrated in vacuo to remove the organic solvent. The resulting residue was purified by a silica gel column chromatography to afford the desired product 2-((4-amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-5-methyl-3-o-tolylthieno[2,3-d]pyrimidin-4(3H)-one (2407) (22.8 mg, 48.2% yield) as a yellow solid.

Workup

  1. customThe resulting mixture was degassed
  2. additionback-filled with argon three times
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. customto remove the organic solvent
  5. customThe resulting residue was purified by a silica gel column chromatography

Sources & evidence

ORD record
ord-7d10a71e39be43839f456a6a115793ba
Source dataset
uspto-grants-2014_04
Patent number
US08703777B2

Reaction notes

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