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

HRID 1431387Notes

Reaction equation

HRID 1431387 reaction equation
[CH3:1][C:2]1([CH3:21])[CH2:7][N:6]([C:8]2[CH:9]=[C:10]([NH2:20])[C:11]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)=[N:12][CH:13]=2)[CH2:5][CH2:4][O:3]1.Cl[C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][C:31]=2[F:33])[N:26]=[C:25]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][N:35]=2)[C:24]=1[CH3:40].Cl.O1CCOCC1.CN1C(=O)CCC1>>[CH3:1][C:2]1([CH3:21])[O:3][CH2:4][CH2:5][N:6]([C:8]2[CH:9]=[C:10]([NH:20][C:23]3[C:32]4[C:27](=[CH:28][CH:29]=[CH:30][C:31]=4[F:33])[N:26]=[C:25]([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][N:35]=4)[C:24]=3[CH3:40])[C:11]([N:14]3[CH2:15][CH2:16][O:17][CH2:18][CH2:19]3)=[N:12][CH:13]=2)[CH2:7]1

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 13387N-methyl-2-pyrrolidoneHCID 312751,4-DioxaneHCID 596312094-Chloro-5-fluoro-3-methyl-2-(pyridin-2-yl)quinolineHCID 596312285-(2,2-Dimethylmorpholino)-2-morpholinopyridin-3-amine

Product 1

HCID 50907188N-(5-(2,2-dimethyl-4-morpholinyl)-2-(4-morpholinyl)-3-pyridinyl)-5-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinamine

Conditions

Temperature
160 °C

Procedure

Prepared according to Procedure K, method 2 using 5-(2,2-dimethylmorpholino)-2-morpholinopyridin-3-amine (62 mg, 0.213 mmol; described herein), 4-chloro-5-fluoro-3-methyl-2-(pyridin-2-yl)quinoline (58 mg, 0.213 mmol; described herein), 4.0M hydrochloric acid in 1,4-dioxane (50 μL, 0.21 mmol), and NMP (310 μL, 3.2 mmol), and heating in a microwave for 3 h at 160° C. Purification afforded N-(5-(2,2-dimethyl-4-morpholinyl)-2-(4-morpholinyl)-3-pyridinyl)-5-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinamine as a yellow solid. 1H NMR (400 MHz, chloroform-d) δ ppm 8.70 (1H, d, J=4.7 Hz), 7.86-8.04 (4H, m), 7.54-7.66 (2H, m), 7.38 (1H, ddd, J=6.7, 4.7, 2.0 Hz), 7.19 (1H, dd, J=13.7, 7.8 Hz), 6.45 (1H, d, J=2.3 Hz), 3.93 (4H, t, J=4.3 Hz), 3.78-3.87 (2H, m), 3.02-3.31 (6H, m), 2.88 (2H, s), 2.21 (3H, s) 1.24-1.34 (6H, m). Mass Spectrum (ESI) m/e=529.2 (M+1).

Workup

  1. customPrepared
  2. customPurification

Sources & evidence

ORD record
ord-b3af28748ac44f829a56dab5729caf2a
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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