Hydrochloric Acid → N-(5-(2-Amino-4-pyrimidinyl)-2-(4-morpholinyl)phenyl)-2-(2-fluorophenyl)-3-methyl-4-quinolinamine

HRID 1431294Notes

Reaction equation

HRID 1431294 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:17]([CH3:18])=[C:16]([NH:19][C:20]2[CH:21]=[C:22]([C:32]3[CH:37]=[CH:36][N:35]=[C:34]([NH:38]C(=O)C)[N:33]=3)[CH:23]=[CH:24][C:25]=2[N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[N:9]=1.Cl.C(#N)C.[OH-].[Na+]>>[NH2:38][C:34]1[N:33]=[C:32]([C:22]2[CH:23]=[CH:24][C:25]([N:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)=[C:20]([NH:19][C:16]3[C:15]4[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=4)[N:9]=[C:8]([C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=4[F:1])[C:17]=3[CH3:18])[CH:21]=2)[CH:37]=[CH:36][N:35]=1

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 6342AcetonitrileHCID 14798Sodium HydroxideHCID 67508373N-(4-(3-(2-(2-Fluorophenyl)-3-methylquinolin-4-ylamino)-4-morpholinophenyl)pyrimidin-2-yl)acetamide

Product 1

HCID 50906136N-(5-(2-Amino-4-pyrimidinyl)-2-(4-morpholinyl)phenyl)-2-(2-fluorophenyl)-3-methyl-4-quinolinamine

Procedure

A solution of N-(4-(3-(2-(2-fluorophenyl)-3-methylquinolin-4-ylamino)-4-morpholinophenyl)pyrimidin-2-yl)acetamide (20 mg, 36 μmol) and concentrated aq. hydrochloric acid (1.50 mL, 18.0 mmol) in acetonitrile (4.00 mL, 76.6 mmol) was heated to 90° C. After 18 h the pH was made alkaline by addition of sodium hydroxide. The reaction mixture was partitioned between 30 mL ea EtOAc and water. The organic layer was stirred over anhydrous magnesium sulfate, filtered and the filtrate concentrated under reduced pressure to afford a yellow solid. The product was purified by chromatography on silica gel eluting with 5-10% MeOH in DCM to afford a colorless solid. 1H NMR (400 MHz, chloroform-d) δ ppm 8.07-8.27 (2H, m), 7.84 (1H, d, J=8.2 Hz), 7.51-7.67 (3H, m), 7.37-7.49 (2H, m), 7.27 (1H, t, J=7.4 Hz), 7.01-7.23 (5H, m), 6.78 (1H, br. s.), 5.10 (2H, br. s.), 3.87 (4H, t, J=4.5 Hz), 3.11 (4H, br. s.), 2.06-2.21 (3H, m). Mass Spectrum (ESI) m/e=507.2 (M+1).

Workup

  1. customThe reaction mixture was partitioned between 30 mL ea EtOAc and water
  2. filtrationfiltered
  3. concentrationthe filtrate concentrated under reduced pressure
  4. customto afford a yellow solid
  5. customThe product was purified by chromatography on silica gel eluting with 5-10% MeOH in DCM
  6. customto afford a colorless solid

Sources & evidence

ORD record
ord-1f82d1fc257e4c2fa4e203ec113a4ba1
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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