Acetic Acid → 4-[2-(5,8-Difluoroquinazolin-4-ylamino)-ethyl]-phenol

HRID 2386904Notes

Reaction equation

HRID 2386904 reaction equation
[NH2:1][CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.C([C:13]1[C:18]([F:19])=[CH:17][CH:16]=[C:15]([F:20])[C:14]=1[N:21]=[CH:22][N:23]([CH3:25])C)#N.C(O)(=O)C>C(O)C>[F:19][C:18]1[CH:17]=[CH:16][C:15]([F:20])=[C:14]2[C:13]=1[C:25]([NH:1][CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1)=[N:23][CH:22]=[N:21]2

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 5610TyramineHCID 59223042N'-(2-Cyano-3,6-difluorophenyl)-N,N-dimethylformamidine

Product 1

HCID 461839254-[2-(5,8-Difluoroquinazolin-4-ylamino)-ethyl]-phenolYield 78.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of tyramine (2.62 g, 19 mmol), N′-(2-cyano-3,6-difluorophenyl)-N,N-dimethylformamidine (2.0 g, 9.56 mmol), acetic acid (3.4 mL, 60 mmol) and ethanol (50 mL) was heated at 75° C. for 16 h. Upon cooling, the solvent was removed under reduced pressure and the remaining solid was stirred in water for a few minutes, collected by suction filtration and washed with water. The filter cake was dried under vacuum to give 2.25 g (78%) of 4-[2-(5,8-difluoroquinazolin-4-ylamino)-ethyl]-phenol as an off-white solid, M.P. 221-222° C. 1H NMR (d6-DMSO): δ 9.16 (s, 1H), 8.53 (s, 1H), 7.73 (m, 1H), 7.59 (m, 1H), 7.52 (m, 1H), 7.05 (d, J=8.4 Hz, 2H), 6.69 (d, J=8.4 Hz, 2H), 3.74 (q, J=7.8, 5.7 Hz, 2H), 2.84 (t, J=7.8 Hz, 2H). LC/MS: 302.04 (M++1).

Workup

  1. temperatureUpon cooling
  2. customthe solvent was removed under reduced pressure
  3. filtrationcollected by suction filtration
  4. washwashed with water
  5. customThe filter cake was dried under vacuum

Sources & evidence

ORD record
ord-b6e162af2cd0489b96e4da5d795abe45
Source dataset
uspto-grants-2012_09
Patent number
US08268843B2

Reaction notes

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