Sodium Carbonate → 3-(4-amino-1-((8-methyl-2-(2-(trifluoromethyl)phenyl)quinolin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)phenol

HRID 2074504Notes

Reaction equation

HRID 2074504 reaction equation
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[N:4]([CH2:12][C:13]2[C:14]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[C:30]([F:33])([F:32])[F:31])=[N:15][C:16]3[C:21]([CH:22]=2)=[CH:20][CH:19]=[CH:18][C:17]=3[CH3:23])[N:3]=1.[OH:34][C:35]1[CH:36]=[C:37](B(O)O)[CH:38]=[CH:39][CH:40]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:11][C:9]1[N:8]=[CH:7][N:6]=[C:5]2[N:4]([CH2:12][C:13]3[C:14]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=4[C:30]([F:31])([F:32])[F:33])=[N:15][C:16]4[C:21]([CH:22]=3)=[CH:20][CH:19]=[CH:18][C:17]=4[CH3:23])[N:3]=[C:2]([C:39]3[CH:40]=[C:35]([OH:34])[CH:36]=[CH:37][CH:38]=3)[C:10]=12

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2734359(3-hydroxyphenyl)boronic AcidHCID 575561613-iodo-1-((8-methyl-2-(2-(trifluoro-methyl)phenyl)quinolin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Product 1

HCID 575561963-(4-amino-1-((8-methyl-2-(2-(trifluoromethyl)phenyl)quinolin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)phenol

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

Prepared according to Procedure J using 3-iodo-1-((8-methyl-2-(2-(trifluoromethyl)phenyl)quinolin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.1 g, 0.1785 mmol, 1 eq), 3-hydroxyphenylboronic acid (0.0492 g, 0.357 mmol, 2.0 eq), tetrakis(triphenylphosphine)palladium (0.0206 g, 0.0178 mmol, 10 mol %), and sodium carbonate (2M aq. sol, 0.535 mL, 1.07 mmol, 6 eq) in DMF (1 mL). After purification, 3-(4-amino-1-((8-methyl-2-(2-(trifluoromethyl)phenyl)quinolin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)phenol was obtained as light gray solid. The gray solid was suspended in CH2Cl2 and filtered to provide 3-(4-amino-1-((8-methyl-2-(2-(trifluoromethyl)phenyl)quinolin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)phenol [PI3Kδ IC50=8 nM] as off-white solid. 1H NMR (DMSO-d6) δ ppm 9.65 (1 H, s), 8.28 (1 H, s), 8.04 (1 H, s), 7.87 (1 H, d, J=7.8 Hz), 7.74-7.80 (1 H, m), 7.64 (1 H, d, J=7.0 Hz), 7.56-7.61 (2 H, m), 7.50-7.56 (1 H, m), 7.34-7.38 (1 H, m), 7.30 (1 H, t, J=7.8 Hz), 6.94-7.02 (2 H, m), 6.80-6.87 (1 H, m), 5.53 (2 H, s), 2.60 (3 H, s). Mass Spectrum (ESI) m/e=527.2 (M+1).

Workup

  1. customPrepared
  2. customAfter purification

Sources & evidence

ORD record
ord-fc8ffa4db5c54653882b9a27dd3b8ffc
Source dataset
uspto-grants-2011_04
Patent number
US07919498B2

Reaction notes

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