Azetidine → 1-Acetyl-piperidine-4-carboxylic acid {3-[5-(2-azetidin-1-yl-pyridine-3-carbonyl)-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl]-propyl}-(3-chloro-4-methyl-phenyl)-amide

HRID 1374475Notes

Reaction equation

HRID 1374475 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:9]([CH2:21][CH2:22][CH2:23][N:24]2[CH2:31][CH:30]3[CH:26]([CH2:27][NH:28][CH2:29]3)[CH2:25]2)[C:10]([CH:12]2[CH2:17][CH2:16][N:15]([C:18](=[O:20])[CH3:19])[CH2:14][CH2:13]2)=[O:11])[CH:5]=[CH:6][C:7]=1[CH3:8].Cl[C:33]1[N:41]=[CH:40][CH:39]=[CH:38][C:34]=1[C:35](Cl)=[O:36].CC[N:44]([CH:48]([CH3:50])C)[CH:45](C)C.N1CCC1>C(Cl)Cl.C1COCC1>[N:44]1([C:33]2[C:34]([C:35]([N:28]3[CH2:29][CH:30]4[CH2:31][N:24]([CH2:23][CH2:22][CH2:21][N:9]([C:4]5[CH:5]=[CH:6][C:7]([CH3:8])=[C:2]([Cl:1])[CH:3]=5)[C:10]([CH:12]5[CH2:17][CH2:16][N:15]([C:18](=[O:20])[CH3:19])[CH2:14][CH2:13]5)=[O:11])[CH2:25][CH:26]4[CH2:27]3)=[O:36])=[CH:38][CH:39]=[CH:40][N:41]=2)[CH2:45][CH2:50][CH2:48]1

Participants

7

Reactant 4

HCID 10422AzetidineHCID 81531DiisopropylethylamineHCID 27745412-Chloronicotinoyl chlorideHCID 58782555HCID 58782555, compound

Product 1

HCID 694403741-Acetyl-piperidine-4-carboxylic acid {3-[5-(2-azetidin-1-yl-pyridine-3-carbonyl)-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl]-propyl}-(3-chloro-4-methyl-phenyl)-amide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 42b (0.063 g, 0.138 mmol) and 2-chloronicotinoyl chloride (73, 0.027 g, 0.15 mmol) in DCM (3 mL) at RT was added DIPEA (0.05 mL, 0.27 mmol). The mixture was stirred overnight at RT and the solvent was evaporated. The residue as obtained contained 74a and was treated with a solution of azetidine (0.1 mL, excess) in THF (2 mL). The reaction mixture was heated at 800 C with stirring for 4 h. The reaction mixture was cooled to RT and the solvents evaporated in vacuo. The crude product was purified by flash chromatography on silica gel eluting with MeOH (containing 10% NH4OH)/DCM (0 to 4% MeOH/NH4OH). The recovered material was dissolved in DCM and cyclohexane was added which resulted in the separation of an oil. The solvents were decanted and product dried in vacuo to afford 0.045 g of II-356: mp 72.9–74° C.; Anal. calcd. for C33H43ClN6O3 (containing 0.5 mol of H2O): C, 65.69; H, 7.66; N, 12.77. Found: C, 65.99; H, 7.47; N, 12.61; ms (ES+) m/z 607 (M+H)

Workup

  1. customthe solvent was evaporated
  2. customThe residue as obtained
  3. temperatureThe reaction mixture was heated at 800 C
  4. stirringwith stirring for 4 h
  5. temperatureThe reaction mixture was cooled to RT
  6. customthe solvents evaporated in vacuo
  7. customThe crude product was purified by flash chromatography on silica gel eluting with MeOH (containing 10% NH4OH)/DCM (0 to 4% MeOH/NH4OH)
  8. dissolutionThe recovered material was dissolved in DCM
  9. additioncyclohexane was added which
  10. customresulted in the separation of an oil
  11. customThe solvents were decanted
  12. customproduct dried in vacuo
  13. customto afford 0.045 g of II-356

Sources & evidence

ORD record
ord-2cdf2b35e5f843dfa99b18b960f1f9fb
Source dataset
uspto-grants-2007_01
Patent number
US07164019B2

Reaction notes

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