Morpholine → 4-(3-Fluorobenzyl)-N-(2-(5-morpholino-1H-indol-3-yl)ethyl)benzamide

HRID 1777681Notes

Reaction equation

HRID 1777681 reaction equation
C1(P(C2CCCCC2)C2C=CC=CC=2C2C(N(C)C)=CC=CC=2)CCCCC1.CC([O-])(C)C.[Na+].[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1.Br[C:42]1[CH:43]=[C:44]2[C:48](=[CH:49][CH:50]=1)[NH:47][CH:46]=[C:45]2[CH2:51][CH2:52][NH:53][C:54](=[O:69])[C:55]1[CH:60]=[CH:59][C:58]([CH2:61][C:62]2[CH:67]=[CH:66][CH:65]=[C:64]([F:68])[CH:63]=2)=[CH:57][CH:56]=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:68][C:64]1[CH:63]=[C:62]([CH:67]=[CH:66][CH:65]=1)[CH2:61][C:58]1[CH:57]=[CH:56][C:55]([C:54]([NH:53][CH2:52][CH2:51][C:45]2[C:44]3[C:48](=[CH:49][CH:50]=[C:42]([N:35]4[CH2:40][CH2:39][O:38][CH2:37][CH2:36]4)[CH:43]=3)[NH:47][CH:46]=2)=[O:69])=[CH:60][CH:59]=1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 23676156Sodium t-butoxideHCID 86699393HCID 86699393, compound

Product 1

HCID 679741904-(3-Fluorobenzyl)-N-(2-(5-morpholino-1H-indol-3-yl)ethyl)benzamideYield 6.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
100 °C

Procedure

A mixture of palladium acetate (0.004 g; 0.017 mmol) and 2′-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (0.028 g; 0.071 mmol) in dioxane (0.5 mL) was degassed and sonicated for 30 minutes. This solution was then added to a degassed mixture of sodium 2-methylpropan-2-olate (0.024 g; 0.248 mmol), morpholine (0.031 mL; 0.354 mmol) and N-(2-(5-bromo-1H-indol-3-yl)ethyl)-4-(3-fluorobenzyl)benzamide (0.080 g; 0.177 mmol) in dioxane (2 mL). The resulting mixture was stirred at 100° C. for 18 hours and evaporated to dryness. The residue was partitioned between water and ethyl acetate and the organic layer was dried and concentrated under reduced pressure. The crude material was purified twice by flash chromatography on silica gel (eluent 65 to 100% ethyl acetate in heptane and 20 to 100% ethyl acetate in dichloromethane) and by preparative HPLC (method 2) to afford 0.0052 g (6%) of the title compound as a white solid.

Workup

  1. customwas degassed
  2. customsonicated for 30 minutes
  3. customevaporated to dryness
  4. customThe residue was partitioned between water and ethyl acetate
  5. customthe organic layer was dried
  6. concentrationconcentrated under reduced pressure
  7. customThe crude material was purified twice by flash chromatography on silica gel (eluent 65 to 100% ethyl acetate in heptane and 20 to 100% ethyl acetate in dichloromethane) and by preparative HPLC (method 2)

Sources & evidence

ORD record
ord-8144a93adc7045fdafee546652036d8e
Source dataset
uspto-grants-2016_02
Patent number
US09266832B2

Reaction notes

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