Morpholine → 8-Chloro-3-morpholino-1,5-naphthyridine

HRID 40376Notes

Reaction equation

HRID 40376 reaction equation
CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CC(C)([O-])C.[Na+].Br[C:50]1[CH:51]=[N:52][C:53]2[C:58]([CH:59]=1)=[N:57][CH:56]=[CH:55][C:54]=2[Cl:60].[NH:61]1[CH2:66][CH2:65][O:64][CH2:63][CH2:62]1>ClCCl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[Cl:60][C:54]1[CH:55]=[CH:56][N:57]=[C:58]2[C:53]=1[N:52]=[CH:51][C:50]([N:61]1[CH2:66][CH2:65][O:64][CH2:63][CH2:62]1)=[CH:59]2

Participants

8

Reactant 4

HCID 8083MorpholineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 134591373-Bromo-8-chloro-1,5-naphthyridineHCID 23676156Sodium t-butoxide

Product 1

HCID 576911288-Chloro-3-morpholino-1,5-naphthyridineYield 32%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

A round bottom flask under nitrogen atmosphere was charged with Pd2(dba)3 (578 mg, 0.63 mmol), Xantphos (1.1 g, 1.89 mmol), and sodium tert-butoxide (364 mg, 3.79 mmol). This was purged with Argon followed by addition of 3-bromo-8-chloro-1,5-naphthyridine (615 mg, 2.53 mmol), morpholine (0.22 mL, 2.53 mmol), and toluene (1M, 2.53 mL). This was then placed in a preheated oil bath at 80° C. After 2.5 hours, reaction was stopped, cooled to room temp and diluted with Dichloromethane. This was passed over a celite cake and filtrate concentrated to afford brown oil; which was purified by ISCO silica gel chromatography (40 g, 1% MeOH/DCM over 50 mins) to afford 8-chloro-3-morpholino-1,5-naphthyridine (200 mg, 32% yield). MS[M+H]=250.2. Calc'd for C12H12ClN3O=249.7.

Workup

  1. customThis was purged with Argon
  2. customThis was then placed in a preheated oil bath at 80° C
  3. customreaction
  4. concentrationconcentrated
  5. customto afford brown oil
  6. customwhich was purified by ISCO silica gel chromatography (40 g, 1% MeOH/DCM over 50 mins)

Sources & evidence

ORD record
ord-ee0dde5b3cb349d3b7cc0012236d0c62
Source dataset
uspto-grants-2013_09
Patent number
US08524900B2

Reaction notes

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