Sodium Carbonate → 3-(4-Amino-1-((8-methyl-2-o-tolylquinolin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)phenol

HRID 2074505Notes

Reaction equation

HRID 2074505 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[CH3:30])=[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:31][C:32]1[CH:33]=[C:34](B(O)O)[CH:35]=[CH:36][CH:37]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.O.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[CH3:30])=[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:36]3[CH:37]=[C:32]([OH:31])[CH:33]=[CH:34][CH:35]=3)[C:10]=12

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2734359(3-hydroxyphenyl)boronic AcidHCID 452790493-Iodo-1-((8-methyl-2-o-tolylquinolin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Product 1

HCID 575561803-(4-Amino-1-((8-methyl-2-o-tolylquinolin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)phenol

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

Prepared according to Procedure J. A mixture of 3-iodo-1-((8-methyl-2-o-tolylquinolin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (51 mg, 0.1 mmol), 3-hydroxyphenylboronic acid (15.2 mg, 1.1 eq), sodium carbonate (55 mg, 5 eq), tetrakis(triphenylphosphine)palladium (6 mg, 5% mmol) in DMF (1 mL) and water (0.3 mL) was heated to 100° C. under N2 for 4 h. The reaction mixture was cooled to room temperature, filtered and purified by reverse HPLC (MeCN/H2O/0.1% TFA) on C18 to give a white solid [PI3Kδ IC50=7 nM]. 1H-NMR (DMSO-d6) δ 8.37 (s, 1H), 8.35 (s, 1H), 7.86 (d, J=8.2 Hz, 1H), 7.65 (d, J=7.0 Hz, 1H), 7.53 (t, J=7.4 Hz, 1H), 7.31 (t, J=7.8 Hz, 1H), 7.14-7.17 (m, 4H), 6.87-6.97 (m, 4H), 5.63 (s, br, 2H), 2.63 (s, 3H), 1.91 (s, 3H). Mass Spectrum (ESI) m/e=473 (M+1).

Workup

  1. customPrepared
  2. temperatureThe reaction mixture was cooled to room temperature
  3. filtrationfiltered
  4. custompurified by reverse HPLC (MeCN/H2O/0.1% TFA) on C18
  5. customto give a white solid [PI3Kδ IC50=7 nM]

Sources & evidence

ORD record
ord-ae37e90d205949f0b5cbc5e58cd5f337
Source dataset
uspto-grants-2011_04
Patent number
US07919498B2

Reaction notes

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