Dimethylamine → Dimethyl{2-[4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenoxymethyl]-quinolin-4-yl}-amine

HRID 1170348Notes

Reaction equation

HRID 1170348 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([CH2:12][O:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[C:24]([C:25]4[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=4)=[CH:23][N:22]([CH3:31])[N:21]=3)=[CH:16][CH:15]=2)[CH:3]=1.[CH3:32][NH:33][CH3:34].[F-].[Cs+].C(N(C(C)C)CC)(C)C>O1CCCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH3:32][N:33]([CH3:34])[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([CH2:12][O:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[C:24]([C:25]4[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=4)=[CH:23][N:22]([CH3:31])[N:21]=3)=[CH:16][CH:15]=2)[CH:3]=1

Participants

7

Reactant 4

HCID 674DimethylamineHCID 25953Cesium fluorideHCID 81531DiisopropylethylamineHCID 115970894-Chloro-2-[4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenoxymethyl]-quinoline

Product 1

HCID 11711771Dimethyl{2-[4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenoxymethyl]-quinolin-4-yl}-amine

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
180 °C

Procedure

To a solution of 4-Chloro-2-[4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenoxymethyl]-quinoline (135 mg) in tetrahydrofuran (4 mL) was added dimethylamine (2N in methanol, 0.32 mL), cesium fluoride (5 mg), diisopropyl ethyl amine (62 mg) and tetrabutyl ammonium iodide (12 mg). The reaction mixture was heated in a microwave reactor at 180° C. with 100 W of power for 40 min. The reaction mixture was filtered through celite and concentrated. Purification via MPLC biotage chromatography, eluting with 5% methanol/1% ammonium hydroxide/methylene chloride provided the title compound (36 mg). 1H NMR (400 MHz, CDCl3) δ 8.45 (d, J=6.2 Hz, 2H), 8.04 (d, J=8.3 Hz, 1H), 7.99 (d, J=8.3 Hz, 1H), 7.62 (m, 1H), 7.56 (s, 1H), 7.42 (m, 1H), 7.38 (d, J=9.1 Hz, 2H), 7.15 (d, J=6.2 Hz, 2H), 7.01 (m, 3H), 5.29 (s, 2H), 3.95 (s, 3H), 3.03 (s, 6H); MS: (M+H m/z=436.3).

Workup

  1. filtrationThe reaction mixture was filtered through celite and
  2. concentrationconcentrated
  3. customPurification via MPLC biotage chromatography
  4. washeluting with 5% methanol/1% ammonium hydroxide/methylene chloride

Sources & evidence

ORD record
ord-27a833ca238b430a9da9f7d32113cd6b
Source dataset
uspto-grants-2010_11
Patent number
US07825254B2

Reaction notes

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