1,2-Dimethoxyethane → HCID 178488189, compound

HRID 897972Notes

Reaction equation

HRID 897972 reaction equation
I[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.C[C:26]1([CH3:49])C(C)(C)OB([C:33]2[CH:48]=[CH:47][C:36]([CH2:37][N:38]3[C:42]4[CH:43]=[CH:44][CH:45]=[CH:46][C:41]=4[N:40]=[CH:39]3)=[CH:35][CH:34]=2)[O:27]1.C(=O)([O-])[O-:51].[Na+].[Na+].[CH3:56][O:57]CCOC>O>[C:26]([OH:51])(=[O:27])[CH3:49].[NH3:3].[N:38]1([CH2:37][C:36]2[CH:35]=[CH:34][C:33]([C:2]3[C:10]4[C:5](=[N:6][CH:7]=[N:8][C:9]=4[NH2:11])[N:4]([C@H:12]4[CH2:17][CH2:16][C@H:15]([N:18]5[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]5)[CH2:14][CH2:13]4)[N:3]=3)=[CH:48][C:47]=2[O:57][CH3:56])[C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][C:41]=2[N:40]=[CH:39]1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 22347008HCID 22347008, compoundHCID 178481015HCID 178481015, compound

Product 2

HCID 12432Ammonia acetateHCID 178488189HCID 178488189, compoundYield 15%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

trans-3-Iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (200 mg, 0.453 mmol), 1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl]-1H-benzo[d]imidazole (303 mg, 0.906 mmol), palladium tetrakistriphenyphosphine (0.31 mg, 0.027 mmol) and sodium carbonate (155 mg, 1.09 mmol) were mixed with ethylene glycol dimethyl ether (5 mL) and water (2.5 mL). The reaction mixture was heated at reflux overnight under nitrogen. The solvent was removed and the residue was purified by reverse phase preparative HPLC (Rainin HPLC, Column: Thermoquest, hyperprep HS C18, 8 um, 250×21.2 mm. Eluents: 5% B/A to 100% B/A in 25 min. (B: acetonitrile, A: 50 mM ammonia acetate buffer, pH 4.5), 21 mL/min.) to give trans-3-[4-(1H-benzo[d]imidazol-1-ylmethyl)-3-methoxyphenyl]-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (35 mg, 15%). 1H NMR (DMSO-d6) δ 1.46 (m, 2H), 1.95 (m, 10H), 2.13 (s, (3H), 2.32 (m, 5H), 4.62 (m, 1H), 5.78 (s, 2H), 7.22 (m, 2H), 7.49 (m, 2H), 7.62 (m, 4H), 8.22 (s, 1H), 8.44 (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+=522.3, Rt=0.82 min.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux overnight under nitrogen
  3. customThe solvent was removed
  4. customthe residue was purified by reverse phase preparative HPLC (Rainin HPLC, Column

Sources & evidence

ORD record
ord-9f8a55cbdeba4147a3883ee8d222ea4f
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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