Morpholine → HCID 66604368, compound

HRID 2410886Notes

Reaction equation

HRID 2410886 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:32]([NH2:34])=[O:33])[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][S:27](=[O:31])(=[O:30])[CH2:26][CH2:25]2)[CH:17]=4)=[CH:7][C:6]=1[Cl:35].[NH:36]1[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[Cl:35][C:6]1[CH:7]=[C:8]([C:11]2[CH:12]=[C:13]([C:32]([NH2:34])=[O:33])[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][S:27](=[O:31])(=[O:30])[CH2:26][CH2:25]2)[CH:17]=4)[CH:9]=[CH:10][C:5]=1[O:4][CH2:3][CH2:2][N:36]1[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1

Participants

5

Reactant 3

HCID 8083MorpholineHCID 11430Potassium CarbonateHCID 66604575HCID 66604575, compound

Product 1

HCID 66604368HCID 66604368, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

3-(4-(2-Bromoethoxy)-3-chlorophenyl)-7-(1,1-dioxo-thiomorpholino)-9H-carbazole-1-carboxamide (48.6 mg, 0.076 mmol, Example 408C) was dissolved in DMF (5 ml). Morpholine (0.1 ml, 1.15 mmol) and K2CO3 (40 mg, 0.29 mmol) were added and the mixture heated to 75° C. for 2 hour. The mixture was filtered through a 0.45 um Nylon filter and purified by prep HPLC. Product containing fractions were evaporated to dryness to give 43.0 mg 3-(3-chloro-4-(2-morpholinoethoxy)phenyl)-7-(1,1-dioxo-thiomorpholino)-9H-carbazole-1-carboxamide. MS (ESI) m/e+=583/585, m/e−=581/583 [1 Cl isotope pattern]. HPLC retention time 14.31 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 11.12 (s, 1H), 8.53 (d, 1H, J=1.2), 8.35 (b, 1H), 8.16 (d, 1H, J=1.5), 8.11 (d, 1H, J=8.8), 7.99 (d, 1H, J=2.3), 7.82 (dd, 1H, J=8.5, 2.2), 7.53 (b, 1H), 7.34 (d, 1H, J=2.0), 7.31 (d, 1H, J=8.8), 7.00 (dd, 1H, J=8.8, 2.2), 4.26 (t, 2H, J=5.8), 3.85 (b, 4H), 3.64-3.59 (m, 4H), 3.23 (b, 4H), 2.79 (t, 2H, J=5.8), 2.58-2.54 (m, 4H).

Workup

  1. filtrationThe mixture was filtered through a 0.45 um Nylon
  2. filtrationfilter
  3. custompurified by prep HPLC
  4. additionProduct containing fractions
  5. customwere evaporated to dryness

Sources & evidence

ORD record
ord-6071f67e44e34537bddeec74cea32cc2
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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