1,2-Dimethoxyethane → HCID 178488238, compound

HRID 897752

Reaction equation

HRID 897752 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.[F:25][C:26]1[C:27](B2OC(C)(C)C(C)(C)O2)=[CH:28][C:29]([O:40][CH3:41])=[C:30]([NH:32][C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36])[CH:31]=1.C(=O)([O-])[O-].[Na+].[Na+].COCCOC>O>[NH2:11][C:9]1[N:8]=[CH:7][N:6]=[C:5]2[N:4]([C@H:12]3[CH2:17][CH2:16][C@H:15]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)[CH2:14][CH2:13]3)[N:3]=[C:2]([C:27]3[C:26]([F:25])=[CH:31][C:30]([NH:32][C:33](=[O:39])[O:34][C:35]([CH3:36])([CH3:37])[CH3:38])=[C:29]([O:40][CH3:41])[CH:28]=3)[C:10]=12

Participants

6

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 223469344-(Boc-amino)-2-fluoro-5-methoxybenzeneboronic acid pinacol esterHCID 178481015HCID 178481015, compound

Product 1

HCID 178488238HCID 178488238, compoundYield 35%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

trans-3-iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.60 g, 1.36 mmol), tert-butyl N-[5-fluoro-2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (1.0 g, 2.72 mmol), palladium tetrakistriphenyphosphine(0.094 g, 0.082 mmol) and sodium carbonate (0.35 g, 3.27 mmol) were mixed with ethylene glycol dimethyl ether (14 mL) and water (7 mL). The reaction mixture was heated at reflux overnight. Organic solvent was removed under reduced pressure and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with water then brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography using dichloromethane/methanol (95:5 to 70:30) as mobile phase to give trans-tert-butyl N-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-5-fluoro-2-methoxyphenyl)carbamate (0.264 g, 35%). 1H NMR (DMSO-d6) δ 1.49 (s, 9H), 1.97 (m, 6H), 2.16 (s, 3H), 2.33 (m, 5H), 2.53 (m, 4H), 3.84 (s, 3H), 4.64 (m, 1H), 7.60 (d, J=6.78 Hz, 1H), 7.83 (d, J=11.96 Hz, 1H), 8.20 (s, 1H), 8.24 (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+=555.3, Rt=2.00 min.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux overnight
  3. customOrganic solvent was removed under reduced pressure
  4. extractionthe aqueous layer was extracted with dichloromethane
  5. washThe combined organic layer was washed with water
  6. dry with materialbrine, dried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-83e22ce7f9fc44aebe9c3e14941ee31a
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Linked notes

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