Cesium carbonate → HCID 54766715, compound

HRID 2361308Notes

Reaction equation

HRID 2361308 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][N:7]([C:12]3[C:13]([CH3:35])=[C:14]([C:18]4[C:30]5[C:29]6[C:24](=[CH:25][C:26]([OH:31])=[CH:27][CH:28]=6)[NH:23][C:22]=5[C:21]([C:32]([NH2:34])=[O:33])=[N:20][CH:19]=4)[CH:15]=[CH:16][CH:17]=3)[C:8]2=[O:11])=[CH:4][CH:3]=1.[C:36](=[O:39])([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.C(OCC)(=O)C>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][N:7]([C:12]3[C:13]([CH3:35])=[C:14]([C:18]4[C:30]5[C:29]6[C:24](=[CH:25][C:26]([O:31][CH2:5][CH2:6][N:7]7[CH2:12][CH2:36][O:39][CH2:9][CH2:8]7)=[CH:27][CH:28]=6)[NH:23][C:22]=5[C:21]([C:32]([NH2:34])=[O:33])=[N:20][CH:19]=4)[CH:15]=[CH:16][CH:17]=3)[C:8]2=[O:11])=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 10796Cesium carbonateHCID 178422184HCID 178422184, compound

Product 1

HCID 54766715HCID 54766715, compoundYield 21.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-(3-(6-chloro-1-oxoisoindolin-2-yl)-2-methylphenyl)-7-hydroxy-9H-pyrido[3,4-b]indole-1-carboxamide (50 mg, 0.104 mmol), 4-(2-chloroethyl)morpholine, HCl (67.4 mg, 0.362 mmol), and cesium carbonate (202 mg, 0.621 mmol) in DMF (6 mL) was heated at 100° C. for 3 hr. The mixture was diluted with ethyl acetate (100 mL) and filtered through CELITE®. The filtrate was washed with water (2×30 mL) and brine (30 mL), and dried over anhydrous MgSO4. After the solvent was removed under vacuum, the residue was purified by reverse phase HPLC. The correct fractions were concentrated under vacuum, basified with saturated NaHCO3 solution, and extracted with ethyl acetate (3×30 mL). The combined extract was washed with brine (30 mL) and dried over anhydrous MgSO4. Removal of solvent under vacuum provided the purified product (7.1 mg, 0.011 mmol, 10.9% yield) as a pale yellow sold. LCMS (M+H)+=596.29. 1H NMR (500 z, DMSO-d6) δ: 11.72 (s, 1H), 8.36 (s, 1H), 8.25 (s, 1H), 7.86 (s, 1H), 7.82-7.78 (m, 3H), 7.72 (d, J=6.9 Hz, 1H), 7.59 (m, 1H), 7.50 (m, 1H), 7.43 (s, 1H), 7.22 (br. S, 1H), 6.79 (br. S, 1H), 5.10 (d, J=17.6 Hz, 1H), 5.00 (d, J=17.6 Hz, 1H), 4.23 (m, 2H), 3.81-3.53 (m, 8H), 2.81 (m, 2H), 1.92 (s, 3H).

Workup

  1. filtrationfiltered through CELITE®
  2. washThe filtrate was washed with water (2×30 mL) and brine (30 mL)
  3. dry with materialdried over anhydrous MgSO4
  4. customAfter the solvent was removed under vacuum
  5. customthe residue was purified by reverse phase HPLC
  6. concentrationThe correct fractions were concentrated under vacuum
  7. extractionextracted with ethyl acetate (3×30 mL)
  8. extractionThe combined extract
  9. washwas washed with brine (30 mL)
  10. dry with materialdried over anhydrous MgSO4
  11. customRemoval of solvent under vacuum

Sources & evidence

ORD record
ord-c428d9f60af349b2bc0b65699b30d83d
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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