Hydrochloric Acid → HCID 66604099, compound

HRID 2410878Notes

Reaction equation

HRID 2410878 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:15]2[CH:16]=[C:17]([C:32]([NH2:34])=[O:33])[C:18]3[NH:19][C:20]4[C:25]([C:26]=3[CH:27]=2)=[CH:24][CH:23]=[C:22]([C:28](O)([CH3:30])[CH3:29])[CH:21]=4)[CH:5]=[CH:6][C:7]=1[CH2:8][N:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1.Cl.[NH:36]1[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C:15]2[CH:16]=[C:17]([C:32]([NH2:34])=[O:33])[C:18]3[NH:19][C:20]4[C:25]([C:26]=3[CH:27]=2)=[CH:24][CH:23]=[C:22]([C:28]([N:36]2[CH2:41][CH2:40][O:39][CH2:38][CH2:37]2)([CH3:30])[CH3:29])[CH:21]=4)[CH:5]=[CH:6][C:7]=1[CH2:8][N:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 8083MorpholineHCID 66604340HCID 66604340, compound

Product 1

HCID 66604099HCID 66604099, compoundYield 24.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-(3-Chloro-4-(morpholinomethyl)phenyl)-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamide (40.3 mg, 0.080 mmol, Example 399) was suspended in HCl (1 M solution in diethyl ether) (5 ml, 5.00 mmol) and sonicated briefly. (not completely dissolved. DCM was added (5 ml) in an unsuccessful attempt to dissolve more). The suspension was stirred at room temperature for 1 hour, then cooled to 0° C. Morpholine (5 ml, 57 4 mmol) was added, the ice bath removed and the mixture stirred at room temperature for 3 days. The reaction mixture was poured into a separating funnel that is loaded with EtOAc and sat. aq. NaHCO3 solution. Layers were separated, the aqueous extracted once more with EtOAc and the organic layer washed with brine, then dried over MgSO4, filtered and evaporated. The crude was purified by prep HPLC. Product containing fractions were filtered through a Waters MCX cartridge (1 g adsorbent), washed with MeOH and the product eluted with a 2M solution of NH3 in MeOH. Evaporation to dryness under a stream of nitrogen gave 10.8 mg white 3-(3-chloro-4-(morpholinomethyl)phenyl)-7-(2-morpholinopropan-2-yl)-9H-carbazole-1-carboxamide. MS (ESI) m/e−=545, m/e+=547 consistent with [M−H]− and [M+H]+. HPLC retention time 5.60 min. (Sunfire C18 3.5 μm, 3.0×150 mm column, 15 min gradient, 10-100% B, 0.5 mL/min. Solvent A: 5% CH3CN—95% H2O—0.1% TFA; Solvent B: 95% CH3CN—5% H2O—0.1% TFA). 1H NMR (CD3OD) δ ppm 8.50 (d, 1H, J=1.7), 8.17 (d, 1H, J=1.5), 8.12 (d, 1H, J=8.3), 7.87 (d, 1H, J=1.7), 7.80 (d, 1H, J=0.7), 7.74 (dd, 1H, J=8.0, 1.8), 7.61 (d, 1H, J=8.1), 7.52 (dd, 1H, J=8.2, 1.6), 3.75-3.68 (m, 10H), 2.61-2.54 (m, 8H), 1.49 (s, 6H).

Workup

  1. customsonicated briefly
  2. dissolution(not completely dissolved
  3. dissolutionto dissolve more)
  4. temperaturecooled to 0° C
  5. customthe ice bath removed
  6. stirringthe mixture stirred at room temperature for 3 days
  7. additionThe reaction mixture was poured into a separating funnel that
  8. customLayers were separated
  9. extractionthe aqueous extracted once more with EtOAc
  10. washthe organic layer washed with brine
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. customevaporated
  14. customThe crude was purified by prep HPLC
  15. additionProduct containing fractions
  16. filtrationwere filtered through a Waters MCX cartridge (1 g adsorbent)
  17. washwashed with MeOH
  18. washthe product eluted with a 2M solution of NH3 in MeOH
  19. customEvaporation to dryness under a stream of nitrogen

Sources & evidence

ORD record
ord-69c694ad82284606a43b5d5b1ae6d891
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

Loading…