Diisopropylethylamine → HCID 86717922, compound

HRID 2275836Notes

Reaction equation

HRID 2275836 reaction equation
Cl.Cl.[NH:3]1[CH2:6][CH:5]([N:7]2[CH2:11][CH2:10][CH2:9][CH2:8]2)[CH2:4]1.[C:12]([NH:19][CH2:20][CH2:21]Br)([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].C(N(CC)C(C)C)(C)C>CO.C(#N)C>[N:7]1([CH:5]2[CH2:6][N:3]([CH2:21][CH2:20][NH:19][C:12](=[O:13])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH2:4]2)[CH2:11][CH2:10][CH2:9][CH2:8]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 4103526tert-Butyl N-(2-bromoethyl)carbamateHCID 19423677Pyrrolidine, 1-(3-azetidinyl)-, dihydrochloride3×

Product 1

HCID 86717922HCID 86717922, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

595 mg of 1-(azetidin-3-yl)pyrrolidine dihydrochloride (Example 219A, 2.75 mmol, purity about 92%, 1 equivalent) were reacted in 3 batches. To obtain the free base, the 1-(azetidin-3-yl)pyrrolidine dihydrochloride was passed over a StratoSpheres™ SPE column. To this end, the column was initially moistened with 1 ml of methanol. 1-(Azetidin-3-yl)pyrrolidine dihydrochloride, dissolved in 3 ml of methanol, was then passed over the column and the column was rinsed with 3 ml of methanol. The solution obtained was concentrated (the column retains about 0.9 mmol of salt). The free base was then initially charged in 26.8 ml of acetonitrile, 656 mg of 2-(Boc-amino)ethyl bromide (2.9 mmol, 1.05 equivalents) and 1.45 ml of N,N-diisopropylethylamine (8.25 mmol, 3 equivalents) were added and the mixture was stirred at 80° C. overnight. The reaction mixture was concentrated and purified by silica gel chromatography (mobile phase: cyclohexane/ethyl acetate 5:1; dichloromethane/methanol 10:1; dichloromethane/methanol 4:1 and dichloromethane/1 N ammonia in methanol 4:1). This gave 463 mg (67% of theory) of the title compound.

Workup

  1. customTo obtain the free base
  2. washthe column was rinsed with 3 ml of methanol
  3. customThe solution obtained
  4. concentrationwas concentrated (the column
  5. concentrationThe reaction mixture was concentrated
  6. custompurified by silica gel chromatography (mobile phase: cyclohexane/ethyl acetate 5:1; dichloromethane/methanol 10:1; dichloromethane/methanol 4:1 and dichloromethane/1 N ammonia in methanol 4:1)

Sources & evidence

ORD record
ord-ae5e57909f3349b1a5f2cc7a8454260f
Source dataset
uspto-grants-2015_09
Patent number
US09126998B2

Reaction notes

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