Morpholine → 2-[2-({3-[4-(morpholine-4-carbonyl)phenoxy]propyl}-pyridin-4-ylmethylamino)ethyl]-2H-isoquinolin-1-one dihydrochloride

HRID 69013Notes

Reaction equation

HRID 69013 reaction equation
Br[C:2]1[CH:32]=[CH:31][C:5]([O:6][CH2:7][CH2:8][CH2:9][N:10]([CH2:24][C:25]2[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=2)[CH2:11][CH2:12][N:13]2[CH:22]=[CH:21][C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]2=[O:23])=[CH:4][CH:3]=1.[C:33](=[O:36])([O-])[O-].[Na+].[Na+].[NH:39]1[CH2:44][CH2:43][O:42][CH2:41][CH2:40]1.C(OC(=O)C)C.[ClH:51]>C(=[Mo](=C=O)(=C=O)(=C=O)(=C=O)=C=O)=O.CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC(O)=O.CC(O)=O.[Pd].[Pd].C(OCC)(=O)C.O.C1COCC1>[ClH:51].[ClH:51].[N:39]1([C:33]([C:2]2[CH:3]=[CH:4][C:5]([O:6][CH2:7][CH2:8][CH2:9][N:10]([CH2:24][C:25]3[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=3)[CH2:11][CH2:12][N:13]3[CH:22]=[CH:21][C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[C:14]3=[O:23])=[CH:31][CH:32]=2)=[O:36])[CH2:44][CH2:43][O:42][CH2:41][CH2:40]1

Participants

10

Reactant 4

HCID 8083MorpholineHCID 10340Sodium CarbonateHCID 21866389Hydrogen chloride-ethyl acetateHCID 669599672-(2-{[3-(4-Bromophenoxy)propyl]pyridin-4-ylmethylamino}ethyl)-2H-isoquinolin-1-one

Product 1

HCID 669600602-[2-({3-[4-(morpholine-4-carbonyl)phenoxy]propyl}-pyridin-4-ylmethylamino)ethyl]-2H-isoquinolin-1-one dihydrochloride

Reagents, catalysts & solvents 5

HCID 11104995trans-Bis(acetato)bis[2-[bis(2-methylphenyl)phosphino]benzyl]dipalladium(II)CatalystHCID 178521658HCID 178521658, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
170 °C

Procedure

2-(2-{[3-(4-Bromophenoxy)propyl]pyridin-4-ylmethylamino}ethyl)-2H-isoquinolin-1-one (500 mg), hexacarbonyl molybdenum (264 mg), trans-di-μ-acetatobis[2-(di-o-tolylphosphino)benzyl]dipalladium (II) (Herrmann's palladacycle)(23 mg), sodium carbonate (318 mg), and morpholine (0.26 ml) were added to THF (5 ml). The mixture was heated at 170° C. for 10 minutes (microwave reactor). The reaction mixture was cooled to room temperature. Water and ethyl acetate were added thereto, followed by celite filtration. The organic layer was dried with sodium sulfate, and condensed under reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate:methanol=1:0→7:3). The purified product was condensed under reduced pressure. A 4N-hydrogen chloride ethyl acetate solution was added to an ethyl acetate solution of the residue. The precipitated insoluble matter was separated, washed with ethyl acetate, and dried to give the title compound (150 mg) as a white powder.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfollowed by celite filtration
  3. dry with materialThe organic layer was dried with sodium sulfate, and condensed under reduced pressure
  4. customThe residue was purified by NH silica gel column chromatography (ethyl acetate:methanol=1:0→7:3)
  5. customcondensed under reduced pressure
  6. customThe precipitated insoluble matter was separated
  7. washwashed with ethyl acetate
  8. customdried

Sources & evidence

ORD record
ord-45d6a4a53cf54b04bafcdf03335ae721
Source dataset
uspto-grants-2014_09
Patent number
US08822453B2

Reaction notes

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