Morpholine → 3-(3-chloro-4-(2-morpholinoethoxy)phenyl)-7-morpholino-9H-carbazole-1-carboxamide

HRID 2410884Notes

Reaction equation

HRID 2410884 reaction equation
Br[CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:12]=[C:13]([C:30]([NH2:32])=[O:31])[C:14]3[NH:15][C:16]4[C:21]([C:22]=3[CH:23]=2)=[CH:20][CH:19]=[C:18]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[CH:17]=4)=[CH:7][C:6]=1[Cl:33].[NH:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[Cl:33][C:6]1[CH:7]=[C:8]([C:11]2[CH:12]=[C:13]([C:30]([NH2:32])=[O:31])[C:14]3[NH:15][C:16]4[C:21]([C:22]=3[CH:23]=2)=[CH:20][CH:19]=[C:18]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[CH:17]=4)[CH:9]=[CH:10][C:5]=1[O:4][CH2:3][CH2:2][N:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1

Participants

5

Reactant 3

HCID 8083Morpholine2×HCID 11430Potassium CarbonateHCID 666050533-(4-(2-bromoethoxy)-3-chlorophenyl)-7-morpholino-9H-carbazole-1-carboxamide

Product 1

HCID 666052013-(3-chloro-4-(2-morpholinoethoxy)phenyl)-7-morpholino-9H-carbazole-1-carboxamideYield 86.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

3-(4-(2-Bromoethoxy)-3-chlorophenyl)-7-morpholino-9H-carbazole-1-carboxamide (110 mg, 0.146 mmol, Example 407A) was dissolved in DMF (5 ml). Morpholine (0.045 ml, 0.517 mmol) and K2CO3 (66 mg, 0.478 mmol) were added and the mixture heated to 75° C. for 1 hour. Additional morpholine (0.10 ml, 1.148 mmol) was added and the mixture heated for one additional hour. The mixture was concentrated to a volume of ˜1 ml, then diluted with 3 ml DMSO+3 ml MeOH, filtered through a 0.45 um Nylon filter and purified by prep HPLC. Product containing fractions were evaporated to dryness to give 67.8 mg 3-(3-chloro-4-(2-morpholinoethoxy)phenyl)-7-morpholino-9H-carbazole-1-carboxamide. MS (ESI) m/e+=535/537, m/e−=533/535 [1 Cl isotope pattern]. HPLC retention time 15.81 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), then isocratic at 100% B. 1H NMR (DMSO-d6) δ ppm 11.13 (s, 1H), 8.49 (d, 1H, J=1.5), 8.34 (b, 1H), 8.14 (d, 1H, J=1.5), 8.07 (d, 1H, J=8.5), 7.99 (d, 1H, J=2.3), 7.82 (dd, 1H, J=8.6, 2.4), 7.51 (b, 1H), 7.31 (d, 1H, J=8.8), 7.24 (d, 1H, J=2.0), 6.94 (dd, 1H, J=8.8, 2.0), 4.26 (t, 2H, J=5.8), 3.83-3.79 (m, 4H), 3.64-3.59 (m, 4H), 3.22-3.17 (m, 4H), 2.79 (t, 2H, J=5.8), 2.58-2.54 (m, 4H).

Workup

  1. temperaturethe mixture heated for one additional hour
  2. concentrationThe mixture was concentrated to a volume of ˜1 ml
  3. additiondiluted with 3 ml DMSO+3 ml MeOH
  4. filtrationfiltered through a 0.45 um Nylon
  5. filtrationfilter
  6. custompurified by prep HPLC
  7. additionProduct containing fractions
  8. customwere evaporated to dryness

Sources & evidence

ORD record
ord-53bef9a4bc7b45e3850a80aba48ce0df
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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