Triethylamine → 2-[4-(1-Methyl-piperidin-3-yl-amino)-quinazolin-2-yl]-phenol

HRID 2189195Notes

Reaction equation

HRID 2189195 reaction equation
B(Br)(Br)Br.Cl[C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[N:9]=[C:8]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[O:22]C)[N:7]=1.Cl.Cl.[CH3:26][N:27]1[CH2:32][CH2:31][CH2:30][CH:29]([NH2:33])[CH2:28]1.C(N(CC)CC)C>ClCCl.CN(C)C(=O)C>[CH3:26][N:27]1[CH2:32][CH2:31][CH2:30][CH:29]([NH:33][C:6]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[N:9]=[C:8]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[OH:22])[N:7]=2)[CH2:28]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 25134Boron tribromideHCID 177503421-Methylpiperidin-3-amine dihydrochlorideHCID 180716414-Chloro-2-(2-methoxyphenyl)quinazoline

Product 1

HCID 1359215662-[4-(1-Methyl-piperidin-3-yl-amino)-quinazolin-2-yl]-phenolYield 83%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 31374DimethylacetamideSolvent

Procedure

Boron tribromide (7.4 mL, 1 M solution in dichloromethane, 7.4 mmol) was added to a solution of 4-chloro-2-(2-methoxy-phenyl)-quinazoline (0.200 g, 0.739 mmol) in dichloromethane (5 mL) at 0° C. After 24 hours the solution was poured into ice-water (200 mL) and extracted with dichloromethane (2×100 mL). The organic layers were combined, washed with brine (100 mL), dried (MgSO4) and concentrated to give a yellow solid that was used immediately without further purification. Half of the material (0.370 mmol) was dissolved in N,N-dimethylacetamide and 1-methylpiperidine-3-amine dihydrochloride (0.083 g, 0.444 mmol) was added. Triethylamine (258 μL, 1.850 mmol) was added and the reaction was stirred for 1 hour. The mixture was concentrated and purified by ion exchange chromatography on SCX-2 Isolute acidic resin (2 g), eluting with methanol and then 1 M ammonia in methanol. The basic fractions were combined and purified by silica column chromatography, eluting with 10% methanol in dichloromethane, to give the title compound as a yellow solid (0.103 g, 83%).

Workup

  1. extractionextracted with dichloromethane (2×100 mL)
  2. washwashed with brine (100 mL)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customto give a yellow solid that
  6. customwas used immediately without further purification
  7. concentrationThe mixture was concentrated
  8. custompurified by ion exchange chromatography on SCX-2 Isolute acidic resin (2 g)
  9. washeluting with methanol
  10. custompurified by silica column chromatography
  11. washeluting with 10% methanol in dichloromethane

Sources & evidence

ORD record
ord-ca106286ca034438b03770b1500162f8
Source dataset
uspto-grants-2012_12
Patent number
US08324226B2

Reaction notes

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