Oxalyl chloride → HCID 53372764, compound

HRID 1753118Notes

Reaction equation

HRID 1753118 reaction equation
[CH3:1][C:2]1[C:6]([C:7]([OH:9])=O)=[CH:5][O:4][N:3]=1.C(Cl)(=O)C(Cl)=O.[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]23[NH:41][CH2:40][CH2:39][N:24]2[C:25](=[O:38])[C:26]2[N:27]([N:29]=[C:30]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=4)[CH:31]=2)[CH2:28]3)=[CH:19][CH:18]=1>C(Cl)Cl.CN(C=O)C.N1C=CC=CC=1.O>[Cl:16][C:17]1[CH:18]=[CH:19][C:20]([C:23]23[N:41]([C:7]([C:6]4[C:2]([CH3:1])=[N:3][O:4][CH:5]=4)=[O:9])[CH2:40][CH2:39][N:24]2[C:25](=[O:38])[C:26]2[N:27]([N:29]=[C:30]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=4)[CH:31]=2)[CH2:28]3)=[CH:21][CH:22]=1

Participants

8

Reactant 3

HCID 65578Oxalyl chlorideHCID 45896923-Methyl-1,2-oxazole-4-carboxylic acidHCID 67368505HCID 67368505, compound

Product 1

HCID 53372764HCID 53372764, compoundYield 49.1%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 1049PyridineSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To generate the acid chloride: to a chilled suspension of 3-methylisoxazole-4-carboxylic acid (231 mg, 1.8 mmol) in dry CH2Cl2 (3.0 mL) was added oxalyl chloride (0.31 mL, 3.7 mmol) followed by DMF (1 drop). The suspension was stirred at 0° C. for 5 minutes and then at room temperature for 1 hour. The resulting solution was concentrated in vacuo at ambient temperature to yield an oil, dried by stirring under nitrogen. 10a-(4-chlorophenyl)-7-(pyridin-2-yl)-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrazolo[1,5-d]pyrazin-5-one (111 mg, 0.3 mmol) in pyridine (3.5 mL) was added to a mixture of the acid chloride (generated as above, 1.8 mmol) in pyridine (2 mL) at 0° C. and stirred at 0° C. to room temperature for 1 hour. LCMS after this time indicated the reaction was complete. The suspension was then diluted with water (15 mL) and extracted with CH2Cl2 (3×10 mL). The extracts were combined, dried (Na2SO4), filtered and concentrated in vacuo to yield a yellow residue. The material was purified by trituration with EtOAc/hexanes (9:1) to give 10a-(4-chlorophenyl)-1-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-7-(pyridin-2-yl)-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrazolo[1,5-d]pyrazin-5-one (63) as a beige solid (70 mg, yield 49%).

Workup

  1. waitat room temperature for 1 hour
  2. concentrationThe resulting solution was concentrated in vacuo at ambient temperature
  3. customto yield an oil
  4. customdried
  5. stirringby stirring under nitrogen
  6. stirringstirred at 0° C. to room temperature for 1 hour
  7. extractionextracted with CH2Cl2 (3×10 mL)
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto yield a yellow residue
  12. customThe material was purified by trituration with EtOAc/hexanes (9:1)

Sources & evidence

ORD record
ord-b2ccb860674f45a4b5f895c1d6cbe6ab
Source dataset
uspto-grants-2015_10
Patent number
US09163029B2

Reaction notes

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