2-(Methylamino)ethanol → N-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]-5-[2-(methylamino)ethoxy]quinazolin-4-amine

HRID 1864186Notes

Reaction equation

HRID 1864186 reaction equation
[H-].[Na+].[CH3:3][NH:4][CH2:5][CH2:6][OH:7].C1OCCOCCOCCOCCOC1.[Cl:23][C:24]1[CH:25]=[C:26]([NH:38][C:39]2[C:48]3[C:43](=[CH:44][CH:45]=[CH:46][C:47]=3F)[N:42]=[CH:41][N:40]=2)[CH:27]=[CH:28][C:29]=1[O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=1>CC(N(C)C)=O>[Cl:23][C:24]1[CH:25]=[C:26]([NH:38][C:39]2[C:48]3[C:43](=[CH:44][CH:45]=[CH:46][C:47]=3[O:7][CH2:6][CH2:5][NH:4][CH3:3])[N:42]=[CH:41][N:40]=2)[CH:27]=[CH:28][C:29]=1[O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=1

Participants

6

Reactant 4

HCID 80162-(Methylamino)ethanolHCID 24758Sodium hydrideHCID 3633615-Crown-5HCID 57444972N-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]-5-fluoroquinazolin-4-amine

Product 1

HCID 69065361N-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]-5-[2-(methylamino)ethoxy]quinazolin-4-amineYield 45%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

Sodium hydride (60% dispersion in mineral oil, 0.63 g) was added to 2-(methylamino)ethanol (0.95 ml), 15-crown-5 (100 μl) and N-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]-5-fluoroquinazolin-4-amine (1.5 g) in DMA (25 ml) and the reaction heated at 100° C. for 2 hours. The reaction was cooled, quenched with saturated aqueous ammonium chloride solution to pH 7-8. Addition of a small amount of saturated aqueous sodium hydrogen carbonate solution resulted in the formation of a precipitate, which was filtered, washed with water and dried. The solid was purified by chromatography using DCM-5% methanol/7N ammonia as eluent to give N-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]-5-[2-(methylamino)ethoxy]quinazolin-4-amine as a yellow solid (0.27 g, 45%); NMR spectrum (DMSO-d6) 2.40 (s, 3H), 3.02 (t, 2H), 4.35 (t, 2H), 5.28 (s, 2H), 7.12 (d, 1H), 7.25 (d, 1H), 7.31 (d, 1H), 7.37 (m, 1H), 7.57 (d, 1H), 7.71 (dd, 1H), 7.85 (m, 2H), 8.10 (d, 1H), 8.51 (s, 1H), 8.58 (m, 1H), 10.57 (bs, 1H); Mass spectrum MH+ 436.5.

Workup

  1. temperatureThe reaction was cooled
  2. customquenched with saturated aqueous ammonium chloride solution to pH 7-8
  3. additionAddition of a small amount of saturated aqueous sodium hydrogen carbonate solution
  4. customresulted in the formation of a precipitate, which
  5. filtrationwas filtered
  6. washwashed with water
  7. customdried
  8. customThe solid was purified by chromatography

Sources & evidence

ORD record
ord-41d952f83b4c4b4e89571ff22a8d58cb
Source dataset
uspto-grants-2009_12
Patent number
US07625908B2

Reaction notes

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