1,2-Dimethoxyethane → 2-Methoxybenzamide

HRID 897553Notes

Reaction equation

HRID 897553 reaction equation
IC1C2C(=NC=NC=2N)N([C@H]2CC[C@@H](N3CCN(C)CC3)CC2)N=1.C([NH:32][C:33]([C:35]1[CH:40]=[CH:39][C:38](B(O)O)=[CH:37][C:36]=1[O:44][CH3:45])=[O:34])C1C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+].COCCOC>O>[CH3:45][O:44][C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=1[C:33]([NH2:32])=[O:34]

Participants

6

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 223467454-[(Benzylamino)carbonyl]-3-methoxyphenylboronic acidHCID 178481014HCID 178481014, compound

Product 1

HCID 755402-MethoxybenzamideYield 237.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

cis-3-Iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (141 mg, 0.319 mmol), 4-[(benzylamino)carbonyl]-3-methoxyphenylboronic acid (100 mg, 0.351 mmol), palladium tetrakistriphenyphosphine (22 mg, 0.019 mmol) and sodium carbonate (81 mg, 0.765 mmol) were mixed with ethylene glycol dimethyl ether (4 mL) and water (2 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) as mobile phase to give cis-N1-benzyl-4-44-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxybenzamide (126 mg, 71%). 1H NMR (CDCl3) δ 1.83 (m, 6H), 2.34 (s, 3H), 2.45 (m, 11H), 4.02 (s, 3H), 4.43 (d, J=5.66 Hz, 2H), 4.95 (m, 1H), 5.52 (bs, 2H), 7.37 (m, 7H), 8.18 (m, 1H), 8.41 (m, 1H); LC/MS (Micromass-Column: Pecosphere, C18, 3 um, 33×4.6 mm. Eluents: 0% B/A to 100% B/A in 4.5 min.(B: acetonitrile, A: 50 mM ammonia acetate buffer, pH 4.5), 3.5 mL/min.): MH+=555.5, Rt=2.65 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-145dc08b83b64fd1b7d7b249ca434aa4
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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