Cesium carbonate → HCID 86677072, compound

HRID 1520335Notes

Reaction equation

HRID 1520335 reaction equation
O[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1)[N:6]=[C:5]2[NH:18][C:19]1[CH:27]=[CH:26][CH:25]=[CH:24][C:20]=1[C:21]([NH2:23])=[O:22].Cl.Cl[CH2:30][CH2:31][N:32]([CH3:34])[CH3:33].C(=O)([O-])[O-:36].[Cs+].[Cs+]>CN(C=O)C.O>[CH3:33][N:32]([CH3:34])[CH2:31][CH2:30][O:36][N:18]([C:5]1[C:4]2[C:9](=[CH:10][CH:11]=[CH:2][CH:3]=2)[N:8]=[C:7]([C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)[N:6]=1)[C:19]1[C:20]([C:21]([NH2:23])=[O:22])=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 11636816N,N-Dimethylaminoethyl chloride hydrochlorideHCID 67297950HCID 67297950, compound

Product 1

HCID 86677072HCID 86677072, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A suspension of 2-(6-hydroxy-2-(pyridin-3-yl)quinazolin-4-ylamino)benzamide (synthesized as described in Scheme 24) (25 mg, 0.07 mmol), 2-chloro-N,N-dimethylethylamine hydrochloride (20 mg, 0.14 mmol) and cesium carbonate (68.4 mg, 0.21 mmol) in DMF (1 mL) was stirred at 60° C. overnight. The reaction mixture was cooled to room temperature, diluted with water (5 mL) and extracted with dichloromethane (3×5 mL). The combined organic extracts were dried over Na2SO4 and concentrated in vacuo. The crude product was purified by prep-TLC (silica, 2000 micron plate, 95% dichloromethane-5% methanol-0.1% NH4OH) to yield the desired compound as a brown solid (12.6 mg, 40%). LCMS m/z=428.9 (M+1) (Method C) (retention time=1.41 min). 1H NMR (300 MHz, DMSO) δ 12.99 (s, 1H), 9.59 (d, J=1.3 Hz, 1H), 9.12 (d, J=8.4 Hz, 1H), 8.81-8.66 (m, 2H), 8.52 (s, 1H), 8.06-7.88 (m, 3H), 7.80-7.53 (m, 4H), 7.22 (t, J=7.6 Hz, 1H), 4.46 (s, 2H), 3.35 (s, 2H), 2.69 (s, 6H).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with dichloromethane (3×5 mL)
  3. dry with materialThe combined organic extracts were dried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by prep-TLC (silica, 2000 micron plate, 95% dichloromethane-5% methanol-0.1% NH4OH)

Sources & evidence

ORD record
ord-5532f40920b44d2e9e912bbc82636eab
Source dataset
uspto-grants-2015_07
Patent number
US09073890B2

Reaction notes

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