Hydrochloric Acid → HCID 118159918, compound

HRID 628343Notes

Reaction equation

HRID 628343 reaction equation
[C:1]([CH:3]=[C:4]1[CH2:7][N:6](C(OC(C)(C)C)=O)[CH2:5]1)#[N:2].N12CCCN=C1CCCCC2.[CH2:26]([N:33]1[C:37]2[CH:38]=[CH:39][C:40]3[N:41]([C:42]([CH3:45])=[N:43][N:44]=3)[C:36]=2[CH:35]=[C:34]1[C:46]1[NH:50][N:49]=[CH:48][CH:47]=1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.Cl.O1CCOCC1>C(#N)C>[CH2:26]([N:33]1[C:37]2[CH:38]=[CH:39][C:40]3[N:41]([C:42]([CH3:45])=[N:43][N:44]=3)[C:36]=2[CH:35]=[C:34]1[C:46]1[CH:47]=[CH:48][N:49]([C:4]2([CH2:3][C:1]#[N:2])[CH2:5][NH:6][CH2:7]2)[N:50]=1)[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 457892161-(tert-Butoxycarbonyl)-3-(cyanomethylene)azetidineHCID 118159527HCID 118159527, compound

Product 1

HCID 118159918HCID 118159918, compoundYield 44.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

tert-Butyl 3-(cyanomethylene)azetidine-1-carboxylate (59 mg, 0.30 mmol, prepared as described in WO 2009114512) and 1,8-diazabicyclo[5.4.0]undec-7-ene (23 μL, 0.15 mmol) were added to a solution of 6-benzyl-1-methyl-7-(1H-pyrazol-5-yl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyridine (50 mg, 0.15 mmol, from Example 62) in acetonitrile (2.0 mL). After stirring for 20 minutes, 4.0 M HCl in dioxane (0.50 mL, 2.0 mmol) was added. After a further reaction time of 22 minutes, the solvent was removed in vacuo and the residue was dissolved in MeOH. Aqueous ammonia was added to adjust pH=10. Purification via preparative HPLC-MS (C18 eluting with a gradient of MeCN and H2O containing 0.15% NH4OH) afforded product as a white solid (28 mg, 44%).

Workup

  1. customAfter a further reaction time of 22 minutes, the solvent was removed in vacuo
  2. dissolutionthe residue was dissolved in MeOH
  3. additionAqueous ammonia was added
  4. customPurification via preparative HPLC-MS (C18
  5. washeluting with a gradient of MeCN and H2O containing 0.15% NH4OH)

Sources & evidence

ORD record
ord-db08a2b98a9b422d8dadfa3ea897063d
Source dataset
uspto-grants-2016_04
Patent number
US09309246B2

Reaction notes

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