Water → 10a-(4-chlorophenyl)-7-methyl-5-oxo-N-(2-phenylethyl)-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrazolo[1,5-d]pyrazine-1-carboxamide

HRID 1910935Notes

Reaction equation

HRID 1910935 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]23[NH:21][CH2:20][CH2:19][N:9]2[C:10](=[O:18])[C:11]2[N:12]([N:14]=[C:15]([CH3:17])[CH:16]=2)[CH2:13]3)=[CH:4][CH:3]=1.[N:22]([CH2:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[C:23]=[O:24].O>N1C=CC=CC=1.C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]23[N:21]([C:23]([NH:22][CH2:25][CH2:26][C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)=[O:24])[CH2:20][CH2:19][N:9]2[C:10](=[O:18])[C:11]2[N:12]([N:14]=[C:15]([CH3:17])[CH:16]=2)[CH2:13]3)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 962WaterHCID 160602Phenethyl isocyanateHCID 5840634610a-(4-chlorophenyl)-7-methyl-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrazolo[1,5-d]pyrazin-5-one

Product 1

HCID 5337264310a-(4-chlorophenyl)-7-methyl-5-oxo-N-(2-phenylethyl)-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrazolo[1,5-d]pyrazine-1-carboxamideYield 99%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 10a-(4-chlorophenyl)-7-methyl-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrazolo[1,5-d]pyrazin-5-one (40 mg, 0.13 mmol) in a mixture of pyridine (400 μl) and CH2Cl2 (400 μl) was added (2-isocyanatoethyl)benzene (150 μl) at 0° C. The mixture was let to come back to room temperature. After 1 h the reaction was complete (monitored by LCMS). Water was then added and the mixture extracted with CH2Cl2. The organic fractions were then stirred overnight with PS-trisamine resin to remove the excess of isocyanate. Filtration through a cotton wool plug and concentration in vacuo gave a residue that was purified by flash chromatography (Silica gel, gradient 2:3 acetone/hexane) to give 10a-(4-chlorophenyl)-7-methyl-5-oxo-N-(2-phenylethyl)-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrazolo[1,5-d]pyrazine-1-carboxamide (41) as a white solid (58 mg, yield 99%).

Workup

  1. customto come back to room temperature
  2. extractionthe mixture extracted with CH2Cl2
  3. customto remove the excess of isocyanate
  4. filtrationFiltration
  5. concentrationthrough a cotton wool plug and concentration in vacuo
  6. customgave a residue that
  7. customwas purified by flash chromatography (Silica gel, gradient 2:3 acetone/hexane)

Sources & evidence

ORD record
ord-c34cff0d9b7642a5b003bf37d64ea93f
Source dataset
uspto-grants-2013_12
Patent number
US08604034B2

Reaction notes

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