Azetidine → HCID 178508467, compound

HRID 2373878Notes

Reaction equation

HRID 2373878 reaction equation
[NH2:1][C:2]1[C:3]2[N:4]([C:8]([C@H:25]3[CH2:30][CH2:29][C@H:28]([CH2:31]OS(C4C=CC(C)=CC=4)(=O)=O)[CH2:27][CH2:26]3)=[N:9][C:10]=2[C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH:12]=2)[CH:5]=[CH:6][N:7]=1.[NH:43]1[CH2:46][CH2:45][CH2:44]1>C1COCC1>[N:43]1([CH2:31][C@H:28]2[CH2:29][CH2:30][C@H:25]([C:8]3[N:4]4[CH:5]=[CH:6][N:7]=[C:2]([NH2:1])[C:3]4=[C:10]([C:11]4[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][C:19]5[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=5)[CH:12]=4)[N:9]=3)[CH2:26][CH2:27]2)[CH2:46][CH2:45][CH2:44]1

Participants

4

Reactant 2

HCID 10422AzetidineHCID 178427748HCID 178427748, compound

Product 1

HCID 178508467HCID 178508467, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

General procedure to Examples 33 and 34: A THF solution (3 mL) of trans-toluene-4-sulfonic acid 4-[8-amino-1-(3-benzyloxy-phenyl)imidazo[1,5-a]pyrazin-3-yl]-cyclohexylmethyl ester (200 mg, 0.34 mmol) in a sealed tube was charged with azetidine (8.92 mmol, 510 mg) and stirred at 50° C. for 24 h. The reaction mixture concentrated in vacuo and partitioned b/w EtOAc and sat. NaHCO3. The organic layer was washed with sat. NaHCO3 (2×), water (1×), brine (1×), dried over Na2SO4, filtered, and concentrated to a yellow oil. The crude material was purified by silica gel column chromatography [Jones Flashmaster, 5 g/25 mL cartridge, eluting with CH2Cl2 to 2% ˜7 N NH3 in MeOH/CH2Cl2] to afford trans-3-(4-azetidin-1-ylmethyl-cyclohexyl)-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-8-ylamine as a white solid (130 mg, 82%).

Workup

  1. concentrationThe reaction mixture concentrated in vacuo
  2. custompartitioned b/w EtOAc and sat. NaHCO3
  3. washThe organic layer was washed with sat. NaHCO3 (2×), water (1×), brine (1×)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated to a yellow oil
  7. customThe crude material was purified by silica gel column chromatography [Jones Flashmaster, 5 g/25 mL cartridge, eluting with CH2Cl2 to 2% ˜7 N NH3 in MeOH/CH2Cl2]

Sources & evidence

ORD record
ord-06ebd4aeadf64c6b8027e9a8eb5de46d
Source dataset
uspto-grants-2008_12
Patent number
US07459554B2

Reaction notes

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