1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (5-Benzyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-(4,6-dimethyl-pyrimidin-5-yl)-methanone

HRID 2236056Notes

Reaction equation

HRID 2236056 reaction equation
[CH3:1][C:2]1[C:7]([C:8]([OH:10])=O)=[C:6]([CH3:11])[N:5]=[CH:4][N:3]=1.[CH2:12]([N:19]1[CH2:26][CH:25]2[CH:21]([CH2:22][NH:23][CH2:24]2)[CH2:20]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH2:12]([N:19]1[CH2:26][CH:25]2[CH2:24][N:23]([C:8]([C:7]3[C:2]([CH3:1])=[N:3][CH:4]=[N:5][C:6]=3[CH3:11])=[O:10])[CH2:22][CH:21]2[CH2:20]1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 44543872-Benzyloctahydropyrrolo[3,4-c]pyrroleHCID 149222224,6-Dimethylpyrimidine-5-carboxylic acid

Product 1

HCID 21076218(5-Benzyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-(4,6-dimethyl-pyrimidin-5-yl)-methanoneYield 79.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

step 1—To a mixture of 4,6-dimethyl-pyrimidine-5-carboxylic acid (0.85 g, 5.58 mmol, T. J. Kress et. al. Heterocycles 1994 38:1375) and 4a (1.13 g, 5.58 mmol, C. J. Ohnmacht et al. J. Heterocycl. Chem. 1983 20:321) in DCM (25 mL) at RT was added sequentially EDCI (1.43 g, 6.7 mmol), HOBt (0.9 g, 6.7 mmol) and DIPEA (3.9 mL, 22.34 mmol) and the mixture was stirred overnight at RT. The reaction mixture was washed with 5% NaHCO3 solution, dried (MgSO4) and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel eluting with MeOH (containing 10% NH4OH)/DCM (0 to 4%) to afford 1.5 g of (5-benzyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-(4,6-dimethyl-pyrimidin-5-yl)-methanone: ms (ES+) m/z 337 (M+H)+. To a solution of amide from the previous step (1.5 g, 4.45 mmol) in MeOH (50 mL) was added ammonium formate (2.81 g, 44.58 mmol). Palladium on charcoal previously wetted with MeOH was slowly added and the mixture heated to reflux for 8 h. The catalyst was filtered and solvent evaporated. The residue was purified by flash chromatography on silica gel eluting with MeOH (containing 10% NH4OH)/DCM (0 to 4%) to afford 0.941 g of 44b: ms (ES+) m/z 247 (M+H)+.

Workup

  1. washThe reaction mixture was washed with 5% NaHCO3 solution
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by flash chromatography on silica gel eluting with MeOH (containing 10% NH4OH)/DCM (0 to 4%)

Sources & evidence

ORD record
ord-4905d47650c74e0ca1b0e9e369eeae9a
Source dataset
uspto-grants-2010_05
Patent number
US07714018B2

Reaction notes

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