Cesium carbonate → HCID 59447492, compound

HRID 1518415Notes

Reaction equation

HRID 1518415 reaction equation
C([O-])([O-])=O.[Cs+].[Cs+].F[C:8]1[N:13]=[C:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH:11]=[CH:10][CH:9]=1.Cl.Cl.[S:23]1[C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=2[N:25]=[C:24]1[NH:32][C:33]([C:35]1[CH:36]=[CH:37][CH:38]=[C:39]2[C:44]=1[CH2:43][NH:42][CH2:41][CH2:40]2)=[O:34]>C(OCC)(=O)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[S:23]1[C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=2[N:25]=[C:24]1[NH:32][C:33]([C:35]1[CH:36]=[CH:37][CH:38]=[C:39]2[C:44]=1[CH2:43][N:42]([C:8]1[N:13]=[C:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH:11]=[CH:10][CH:9]=1)[CH2:41][CH2:40]2)=[O:34]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 468355932-Pyridinecarboxylic acid, 6-fluoro-, 1,1-diMethylethyl esterHCID 86644320N-(benzo[d]thiazol-2-yl)-1,2,3,4-tetrahydroisoquinoline-8-carboxamide dihydrochloride

Product 1

HCID 59447492HCID 59447492, compoundYield 29%

Reagents, catalysts & solvents 2

HCID 311Citric AcidSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

Cs2CO3 (831 mg, 2.55 mmol) and 500 mg of 4 Å sieves were dried under high vacuum at 150° C. for 6 hours before the start of the reaction. Once cooled down, compound 120A (100 mg, 0.51 mmol) and compound 1B (327 mg, 0.61 mmol) were transferred to the reaction vessel and the atmosphere was purged with nitrogen. 1.5 mL of anhydrous DMA was then added and the reaction was stirred at 90° C. for 3 hours and then 100° C. for 2 hours. The cooled reaction mixture was then diluted with ethyl acetate and citric acid 10%. The organic phase was washed three times with citric acid, once with water and brine, and dried over Na2SO4. Concentration of the organic phase afforded an orange film/foam. This residue was purified by flash chromatography using SiO2 (AcOEt/Pet. Eth. 0:100 to 40:60). to provide a white solid (72 mg, 29% yield): 1HNMR (ppm, CDCl3) 1.54 (s, 9H), 3.01 (t, J=5.85 Hz, 2H), 4.05 (t, J=6 Hz, 2H), 5.04 (s, 2H), 6.92 (dd, J=8.55 and 0.63 Hz, 1H), 7.09-7.29 (m, 5H), 7.34 (dd, J=7.32 and 0.63 Hz, 1H), 7.60-7.51 (m, 2H), 7.81 (d, J=9 Hz, 1H).

Workup

  1. temperatureOnce cooled down
  2. customthe atmosphere was purged with nitrogen
  3. addition1.5 mL of anhydrous DMA was then added
  4. wait100° C. for 2 hours
  5. customThe cooled reaction mixture
  6. washThe organic phase was washed three times with citric acid
  7. dry with materialonce with water and brine, and dried over Na2SO4
  8. customConcentration of the organic phase afforded an orange film/foam
  9. customThis residue was purified by flash chromatography

Sources & evidence

ORD record
ord-1600b4021f9d4d74b400fdca7b2d231d
Source dataset
uspto-grants-2012_07
Patent number
US08232273B2

Reaction notes

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