Water → 1-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-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

HRID 1910951Notes

Reaction equation

HRID 1910951 reaction equation
C(Cl)(=O)C(Cl)=O.[CH3:7][C:8]1[C:12]([C:13]([OH:15])=O)=[CH:11][O:10][N:9]=1.[N:16]1([CH2:22][CH2:23][O:24][C:25]2[CH:30]=[CH:29][C:28]([C:31]34[NH:43][CH2:42][CH2:41][N:32]3[C:33](=[O:40])[C:34]3[N:35]([CH:37]=[CH:38][CH:39]=3)[CH2:36]4)=[CH:27][CH:26]=2)[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1.O>CN(C=O)C.C(Cl)Cl.N1C=CC=CC=1>[CH3:7][C:8]1[C:12]([C:13]([N:43]2[C:31]3([C:28]4[CH:29]=[CH:30][C:25]([O:24][CH2:23][CH2:22][N:16]5[CH2:17][CH2:18][O:19][CH2:20][CH2:21]5)=[CH:26][CH:27]=4)[CH2:36][N:35]4[CH:37]=[CH:38][CH:39]=[C:34]4[C:33](=[O:40])[N:32]3[CH2:41][CH2:42]2)=[O:15])=[CH:11][O:10][N:9]=1

Participants

8

Reactant 4

HCID 962WaterHCID 65578Oxalyl chlorideHCID 45896923-Methyl-1,2-oxazole-4-carboxylic acidHCID 67368823HCID 67368823, compound

Product 1

HCID 584063391-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-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-oneYield 36%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 1049PyridineSolvent3×HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To generate the acid chloride, oxalyl chloride (0.1 mL, 1.2 mmol) and DMF (1 drop) were added to 3-methyl-1,2-oxazole-4-carboxylic acid (30 mg, 0.24 mmol) in CH2Cl2 (0.5 mL) at 0° C. The suspension was allowed to stir 15 minutes at 0° C. followed by 1 hour at room temperature. The resulting solution was concentrated to give an oil that was further dried under nitrogen. To a chilled suspension of the acid chloride (generated as above, 0.24 mmol) in pyridine (0.5 mL) was added 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 (20 mg, 75% pure, 0.039 mmol) in pyridine (0.3 mL). The reaction mixture was stirred at 0° C. and then at room temperature. After 2.5 hours an additional batch of acid chloride (0.24 mmol) was prepared as above, diluted in pyridine (0.3 mL) and added to the reaction mixture. The mixture was stirred overnight at room temperature. Water (2 mL) was then added and the mixture extracted with dichloromethane (3×1.5 mL). The organic layers were dried (MgSO4), filtrated and concentrated in vacuo to give a residue that was purified by preparative LCMS (reverse phase, acetonitrile-water containing 0.1% formic acid) to give 1-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-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 (110) (7 mg, yield 36%).

Workup

  1. waitfollowed by 1 hour at room temperature
  2. concentrationThe resulting solution was concentrated
  3. customto give an oil that
  4. customwas further dried under nitrogen
  5. stirringThe reaction mixture was stirred at 0° C.
  6. customat room temperature
  7. additionadded to the reaction mixture
  8. stirringThe mixture was stirred overnight at room temperature
  9. extractionthe mixture extracted with dichloromethane (3×1.5 mL)
  10. dry with materialThe organic layers were dried (MgSO4)
  11. filtrationfiltrated
  12. concentrationconcentrated in vacuo
  13. customto give a residue that
  14. customwas purified by preparative LCMS (reverse phase, acetonitrile-water containing 0.1% formic acid)

Sources & evidence

ORD record
ord-30a5f1d5224f4172ac9819108cbe8d7c
Source dataset
uspto-grants-2013_12
Patent number
US08604034B2

Reaction notes

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