Water → HCID 22256600, compound

HRID 1178680Notes

Reaction equation

HRID 1178680 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([O:9][CH3:10])=[CH:4][C:3]=1[NH:11][C:12]1[C:17]([C:18]#[N:19])=[CH:16][N:15]=[C:14]2[CH:20]=[C:21]([C:23]#[C:24][C:25]3[CH:26]=[N:27][NH:28][CH:29]=3)[S:22][C:13]=12.Cl.Cl[CH2:32][CH2:33][N:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([O:9][CH3:10])=[CH:4][C:3]=1[NH:11][C:12]1[C:17]([C:18]#[N:19])=[CH:16][N:15]=[C:14]2[CH:20]=[C:21]([C:23]#[C:24][C:25]3[CH:29]=[N:28][N:27]([CH2:32][CH2:33][N:34]4[CH2:39][CH2:38][O:37][CH2:36][CH2:35]4)[CH:26]=3)[S:22][C:13]=12

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 77210Morpholine, 4-(2-chloroethyl)-, hydrochloride (1:1)HCID 10410968HCID 10410968, compound

Product 1

HCID 22256600HCID 22256600, compoundYield 69.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-(1H-pyrazol-4-ylethynyl)thieno[3,2-b]pyridine-6-carbonitrile (57 mg, 0.13 mmol), 4-(2-chloroethyl)morpholine hydrochloride (24 mg, 0.13 mmol), and cesium carbonate (42 mg, 0.13 mmol) in 1 mL of dimethylformamide is heated at 50° C. overnight. The mixture is cooled to room temperature and then added to water. The resulting precipitate is collected by filtration. The collected solid is purified by flash column chromatography, eluting with 1:7 methanol:ethyl acetate to provide 50 mg of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-{[1-(2-morpholin-4-ylethyl)-1H-pyrazol-4-yl]ethynyl}thieno[3,2-b]pyridine-6-carbonitrile as a yellow solid, mp greater than 200° C.; 1H NMR (DMSO-d6) δ 2.44 (br s, 4H), 2.62 (t, 2H), 3.53 (br s, 4H), 3.81 (s, 3H), 4.23 (br s, 2H), 6.77 (s, 1H), 7.57 (s, 1H), 7.71 (s, 1H), 7.80 (br, 1H), 8.24 (br, 1H), 8.37 (s, 1H), 13.36 (br s, 1H); MS 553.1 (M+H)+.

Workup

  1. temperatureThe mixture is cooled to room temperature
  2. filtrationThe resulting precipitate is collected by filtration
  3. customThe collected solid is purified by flash column chromatography
  4. washeluting with 1:7 methanol

Sources & evidence

ORD record
ord-1bb7dae872f14e9ba1c8e12a7d2d2f74
Source dataset
uspto-grants-2007_10
Patent number
US07276519B2

Reaction notes

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