Hydrochloric Acid → N-(5-(2,2-dimethyl-4-morpholinyl)-2-(4-morpholinyl)-3-pyridinyl)-7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinamine

HRID 1431386Notes

Reaction equation

HRID 1431386 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([F:12])=[CH:9][CH:10]=2)[N:5]=[C:4]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)[C:3]=1[CH3:19].[CH3:20][C:21]1([CH3:40])[CH2:26][N:25]([C:27]2[CH:28]=[C:29]([NH2:39])[C:30]([N:33]3[CH2:38][CH2:37][O:36][CH2:35][CH2:34]3)=[N:31][CH:32]=2)[CH2:24][CH2:23][O:22]1.Cl.O1CCOCC1.CN1C(=O)CCC1>>[CH3:20][C:21]1([CH3:40])[O:22][CH2:23][CH2:24][N:25]([C:27]2[CH:28]=[C:29]([NH:39][C:2]3[C:11]4[C:6](=[CH:7][C:8]([F:12])=[CH:9][CH:10]=4)[N:5]=[C:4]([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=4)[C:3]=3[CH3:19])[C:30]([N:33]3[CH2:34][CH2:35][O:36][CH2:37][CH2:38]3)=[N:31][CH:32]=2)[CH2:26]1

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 13387N-methyl-2-pyrrolidoneHCID 312751,4-DioxaneHCID 596310754-Chloro-7-fluoro-3-methyl-2-(pyridin-2-yl)quinolineHCID 596312285-(2,2-Dimethylmorpholino)-2-morpholinopyridin-3-amine

Product 1

HCID 59631244N-(5-(2,2-dimethyl-4-morpholinyl)-2-(4-morpholinyl)-3-pyridinyl)-7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinamine

Conditions

Temperature
160 °C

Procedure

Prepared according to Procedure K, method 2 using 4-chloro-7-fluoro-3-methyl-2-(pyridin-2-yl)quinoline (66.3 mg, 0.24 mmol; described herein), 5-(2,2-dimethylmorpholino)-2-morpholinopyridin-3-amine (71.0 mL, 0.243 mmol, described herein), 4.0M hydrochloric acid in 1,4-dioxane (60 μL, 0.24 mmol), and NMP (350 μL, 3.6 mmol), and heating in a microwave at 160° C. for 3 h. Purification afforded N-(5-(2,2-dimethyl-4-morpholinyl)-2-(4-morpholinyl)-3-pyridinyl)-7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinamine as a yellow solid. 1H NMR (400 MHz, chloroform-d) δ ppm 8.74 (1H, dd, J=3.5, 1.2 Hz), 7.86-7.95 (2H, m), 7.78-7.86 (2H, m), 7.58 (1H, d, J=2.7 Hz), 7.40 (1H, ddd, J=6.9, 5.0, 1.8 Hz), 7.28-7.33 (1H, m), 6.83 (1H, s), 6.22 (1H, d, J=2.7 Hz), 3.93 (4H, t, J=4.7 Hz), 3.72-3.84 (3H, m), 3.65 (1H, t, J=5.9 Hz), 3.09-3.33 (4H, m), 2.80-2.93 (2H, m), 2.74 (2H, s), 2.37 (3H, s), 1.25-1.31 (4H, m). Mass Spectrum (ESI) m/e=529.2 (M+1).

Workup

  1. customPrepared
  2. customPurification

Sources & evidence

ORD record
ord-90988c876deb4e7caae6b02c3bf6bbfa
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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