Diisopropylethylamine → 1-Cyclobutyl-4-({1-[(6-methylpyridin-3-yl)carbonyl]azetidin-3-yl}carbonyl)piperazine

HRID 1402763Notes

Reaction equation

HRID 1402763 reaction equation
[NH:1]1[CH2:4][CH:3]([C:5]([N:7]2[CH2:12][CH2:11][N:10]([CH:13]3[CH2:16][CH2:15][CH2:14]3)[CH2:9][CH2:8]2)=[O:6])[CH2:2]1.[CH3:17][C:18]1[N:23]=[CH:22][C:21]([C:24](Cl)=[O:25])=[CH:20][CH:19]=1.CCN(C(C)C)C(C)C>ClCCl>[CH:13]1([N:10]2[CH2:11][CH2:12][N:7]([C:5]([CH:3]3[CH2:2][N:1]([C:24]([C:21]4[CH:22]=[N:23][C:18]([CH3:17])=[CH:19][CH:20]=4)=[O:25])[CH2:4]3)=[O:6])[CH2:8][CH2:9]2)[CH2:14][CH2:15][CH2:16]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 218904586-Methylnicotinoyl chlorideHCID 667393151-(Azetidin-3-ylcarbonyl)-4-cyclobutylpiperazine

Product 1

HCID 667394861-Cyclobutyl-4-({1-[(6-methylpyridin-3-yl)carbonyl]azetidin-3-yl}carbonyl)piperazineYield 19.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 1-(azetidin-3-ylcarbonyl)-4-cyclobutylpiperazine (60 mg, 0.27 mmol) in dichloromethane (1 mL) at 0° C., was added 6-methylpyridine-3-carbonyl chloride (31 mg, 0.32 mmol) and DIPEA (142 μL, 0.81 mmol). After 4 hours the reaction was quenched by addition of saturated aq. NaHCO3 (1 mL) and the aqueous extracted with dichloromethane (2×5 mL), dried (MgSO4), filtered, and concentrated at reduced pressure. Purification by silica FCC (eluting with 90:9:1 Et2O/MeOH/NH3) followed by capture and release on an SCX-2 cartridge (washing with MeOH and releasing with 7M NH3 in MeOH) gave the title compound (17.8 mg, 19%)

Workup

  1. customAfter 4 hours the reaction was quenched by addition of saturated aq. NaHCO3 (1 mL)
  2. extractionthe aqueous extracted with dichloromethane (2×5 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated at reduced pressure
  6. customPurification
  7. washby silica FCC (eluting with 90:9:1 Et2O/MeOH/NH3)
  8. washfollowed by capture and release on an SCX-2 cartridge (washing with MeOH and releasing with 7M NH3 in MeOH)

Sources & evidence

ORD record
ord-0527581ea75340cd89dd7708d751041c
Source dataset
uspto-grants-2014_12
Patent number
US08912176B2

Reaction notes

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