1,2-Dimethoxyethane → HCID 20817053, compound

HRID 897964Notes

Reaction equation

HRID 897964 reaction equation
[CH3:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[N:4]([C@H:12]2[CH2:17][CH2:16][C@@H:15]([N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)[CH2:14][CH2:13]2)[N:3]=1.[CH:25]([C:27]1[CH:32]=[CH:31]C(B(O)O)=[CH:29][CH:28]=1)=[O:26].C(=O)([O-])[O-].[Na+].[Na+].COCCOC>O>[NH2:11][C:9]1[N:8]=[CH:7][N:6]=[C:5]2[N:4]([CH:12]3[CH2:17][CH2:16][CH:15]([N:18]4[CH2:19][CH2:20][N:21]([CH3:24])[CH2:22][CH2:23]4)[CH2:14][CH2:13]3)[N:3]=[C:2]([C:1]3[CH:31]=[CH:32][C:27]([CH:25]=[O:26])=[CH:28][CH:29]=3)[C:10]=12

Participants

6

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 5910734-Formylphenylboronic AcidHCID 178434087HCID 178434087, compound

Product 1

HCID 20817053HCID 20817053, compoundYield 54.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

cis-3-Methyl-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (3.0 g, 6.80 mmol), 4-formylphenylboronic acid (1.22 g, 8.16 mmol), palladium tetrakistriphenyphosphine (0.47 g, 0.41 mmol) and sodium carbonate (1.73 g, 16.31 mmol) were mixed with ethylene glycol dimethyl ether (70 mL) and water (35 mL). The reaction mixture was heated at reflux overnight under nitrogen. Organic solvent was removed under reduced pressure and the aqueous layer was filtered and washed with water. After drying on the lyophilizer, the residue was purified by flash column chromatography using dichloromethane/methanol (90:10 to 70:30) as mobile phase to give 4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}benzaldehyde (1.55 g, 54%). 1H NMR (DMSO-d6) δ 1.60 (m, 2H), 1.72 (m, 2H). 2.07 (m, 2H), 2.15 (s, 3H), 2.22-2.46 (m, 1H), 4.83 (m, 1H), 7.88 (d, J=8.13 Hz, 2H), 8.07 (d, J=8.10 Hz, 2H), 8.21 (s, 1H), 10.11 (s, 1H). LCMS (Thermoquest AQA single Quad MS, Finnigan HPLC-Column: Genesis, C18, 3 um, 33×4.6 mm. Eluents: 30% B/A to 95% B/A in 4.5 min. (B: acetonitrile, A: 50 mM ammonia acetate buffer, pH 4.5), 0.8 mL/min.): MH+=420.2, Rt=0.70 min.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux overnight under nitrogen
  3. customOrganic solvent was removed under reduced pressure
  4. filtrationthe aqueous layer was filtered
  5. washwashed with water
  6. customAfter drying on the lyophilizer
  7. customthe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-de64661b550843d3a3ceb016ffa14166
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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