Sodium Carbonate → HCID 136128170, compound

HRID 2074509Notes

Reaction equation

HRID 2074509 reaction equation
ClC1C=CC=CC=1C1C(C[N:20]2[C:24]3=NC=NC(N)=[C:23]3[C:22](I)=[N:21]2)=NC2C(N=1)=CC=CC=2C.[Cl:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=1[C:38]1[C:39]([CH2:49][N:50]2[C:54]3=[N:55][CH:56]=[N:57][C:58]([NH2:59])=[C:53]3[C:52](I)=[N:51]2)=[N:40][C:41]2[C:46]([N:47]=1)=[C:45]([CH3:48])[CH:44]=[CH:43][CH:42]=2.N1C=C(B2OC(C)(C)C(C)(C)O2)C=N1.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>[Cl:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=1[C:38]1[C:39]([CH2:49][N:50]2[C:54]3=[N:55][CH:56]=[N:57][C:58]([NH2:59])=[C:53]3[C:52]([C:23]3[CH:24]=[N:20][NH:21][CH:22]=3)=[N:51]2)=[N:40][C:41]2[C:46]([N:47]=1)=[C:45]([CH3:48])[CH:44]=[CH:43][CH:42]=2

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 57556152HCID 57556152, compoundHCID 57556162HCID 57556162, compound

Product 1

HCID 136128170HCID 136128170, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

Prepared according to Procedure J using a mixture of 1-((3-(2-chlorophenyl)-8-methylquinoxalin-2-yl)methyl)-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine and 1-((3-(2-chlorophenyl)-5-methylquinoxalin-2-yl)methyl)-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.2737 g, 0.52 mmol, 1 eq), 4-pyrazoleboronic acid pinacol ester (0.20 g, 1.0 mmol, 2.0 eq), tetrakis(triphenylphosphine)palladium(0) (0.060 g, 0.052 mmol, 10 mol %), and sodium carbonate (2M aq. sol, 1.6 mL, 3.1 mmol, 6 eq) in DMF (3.1 mL). After purification, a mixture of 1-((3-(2-chlorophenyl)-8-methylquinoxalin-2-yl)methyl)-3-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine and 1-((3-(2-chlorophenyl)-5-methylquinoxalin-2-yl)methyl)-3-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine was obtained as tan solid. The tan solid (0.1566 g) was dissolved in DMSO (8 mL) and purified by semi-prep-HPLC on C18 column using 20-70% gradient of CH3CN (0.1% of TFA) in water (0.1% of TFA) over 40 min as eluent to provide 1-((3-(2-chlorophenyl)-8-methylquinoxalin-2-yl)methyl)-3-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine [PI3Kδ IC50=18 nM] as white solid as a TFA salt and 1-((3-(2-chlorophenyl)-5-methylquinoxalin-2-yl)methyl)-3-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine [PI3Kδ IC50=30 nM] as white solid as a TFA salt. 1H NMR (DMSO-d6) δ ppm 8.18 (1 H, s), 7.88-7.96 (3 H, m), 7.77-7.82 (1 H, m), 7.72-7.77 (1 H, m), 7.49 (1 H, d, J=7.8 Hz), 7.27-7.38 (3 H, m), 5.82 (2 H, d, J=18.4 Hz), 2.54 (3 H, s); Mass Spectrum (ESI) m/e=468.1 (M+1); HPLC: a peak at 6.522 min. 1H NMR (DMSO-d6) δ ppm 8.15 (1 H, s), 7.91-7.96 (1 H, m), 7.89 (2 H, s), 7.78-7.84 (1 H, m), 7.74-7.78 (1 H, m), 7.40-7.49 (1 H, m), 7.18-7.34 (3 H, m), 5.82 (2 H, d, J=27.4 Hz), 2.66 (3 H, s); Mass Spectrum (ESI) m/e=468.1 (M+1); HPLC: a peak at 6.700 min.

Workup

  1. customPrepared
  2. customAfter purification
  3. additiona mixture of 1-((3-(2-chlorophenyl)-8-methylquinoxalin-2-yl)methyl)-3-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Sources & evidence

ORD record
ord-0b3199add5484771afb63bf34ff65cb3
Source dataset
uspto-grants-2011_04
Patent number
US07919498B2

Reaction notes

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