Water → HCID 67368823, compound

HRID 1753173Notes

Reaction equation

HRID 1753173 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]23[NH:20][CH2:19][CH2:18][N:9]2[C:10](=[O:17])[C:11]2[N:12]([CH:14]=[CH:15][CH:16]=2)[CH2:13]3)=[CH:4][CH:3]=1.Cl.Cl[CH2:23][CH2:24][N:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1.C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C.[Cl-].[Na+].O>[N:25]1([CH2:24][CH2:23][O:1][C:2]2[CH:7]=[CH:6][C:5]([C:8]34[NH:20][CH2:19][CH2:18][N:9]3[C:10](=[O:17])[C:11]3[N:12]([CH:14]=[CH:15][CH:16]=3)[CH2:13]4)=[CH:4][CH:3]=2)[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 77210Morpholine, 4-(2-chloroethyl)-, hydrochloride (1:1)HCID 67370128HCID 67370128, compound

Product 1

HCID 67368823HCID 67368823, compoundYield 30.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
100 °C

Procedure

10a-(4-hydroxyphenyl)-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one (50 mg, 0.19 mmol), 4-(2-chloroethyl)morpholine hydrochloride (106 mg, 0.57 mmol) and potassium carbonate (105 mg, 0.76 mmol) were suspended in DMF (1 mL) and the mixture heated at 100° C. The reaction was complete after 3 hours. Brine (5 mL) and water (1 mL) were then added. The mixture was then extracted with ethyl acetate (3×3 mL) and the extracts were combined, dried (MgSO4), filtered and concentrated in vacuo to yield a residue that was purified by flash chromatography (Biotage SP4, gradient 0 to 10% methanol-dichloromethane). The material isolated required a second purification by reverse phase chromatography (Biotage SP4, C18 column, 5 to 100% 10 mM NH4OAC (aq)-MeOH) to give 10a-{4-[2-(morpholin-4-yl)ethoxy]phenyl}-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one (75% pure, 22 mg, yield: 22%). The product was used in the next step without further purification. ESI-MI m/z [M+H]+ 383.2.

Workup

  1. extractionThe mixture was then extracted with ethyl acetate (3×3 mL)
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto yield a residue that
  6. customwas purified by flash chromatography (Biotage SP4, gradient 0 to 10% methanol-dichloromethane)
  7. customThe material isolated
  8. customa second purification by reverse phase chromatography (Biotage SP4, C18 column, 5 to 100% 10 mM NH4OAC (aq)-MeOH)

Sources & evidence

ORD record
ord-313883629a284352ad4db8d1809a3e0d
Source dataset
uspto-grants-2015_10
Patent number
US09163029B2

Reaction notes

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