Ammonia → US10442803, Example 157

HRID 628369Notes

Reaction equation

HRID 628369 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][CH:26]=1)[CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][C:13]3[N:14]([C:15]([CH3:18])=[N:16][N:17]=3)[C:9]=2[CH:8]=[C:7]1[C:19]1[NH:23][N:22]=[CH:21][CH:20]=1.[C:27]([CH:29]=[C:30]1[CH2:33][N:32](C(OC(C)(C)C)=O)[CH2:31]1)#[N:28].N12CCCN=C1CCCCC2.Cl.O1CCOCC1.N>C(#N)C.CO>[Cl:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][CH:26]=1)[CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][C:13]3[N:14]([C:15]([CH3:18])=[N:16][N:17]=3)[C:9]=2[CH:8]=[C:7]1[C:19]1[CH:20]=[CH:21][N:22]([C:30]2([CH2:29][C:27]#[N:28])[CH2:33][NH:32][CH2:31]2)[N:23]=1

Participants

9

Reactant 6

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 457892161-(tert-Butoxycarbonyl)-3-(cyanomethylene)azetidineHCID 118159473US9777003, Example 155

Product 1

HCID 118159592US10442803, Example 157Yield 73%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Procedure

6-(3-Chlorobenzyl)-1-methyl-7-(1H-pyrazol-5-yl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyridine (25 mg, 0.069 mmol, from Example 103, Step 5) in acetonitrile (0.90 mL), was treated with tert-butyl 3-(cyanomethylene)azetidine-1-carboxylate (27 mg, 0.14 mmol, prepared as described in WO 2009114512) and 1,8-diazabicyclo[5.4.0]undec-7-ene (10. μL, 0.069 mmol, Aldrich). After 70 minutes, 4.0 M hydrogen chloride in dioxane (0.23 mL, 0.90 mmol) was added into the reaction. After 30 minutes, the reaction was diluted with methanol, and adjusted to pH˜10 by the addition of a small amount of aqueous ammonia. Purification via preparative HPLC-MS (C18 eluting with a gradient of MeCN/H2O containing 0.15% NH4OH) afforded product (23 mg, 73%).

Workup

  1. waitAfter 30 minutes
  2. customPurification via preparative HPLC-MS (C18
  3. washeluting with a gradient of MeCN/H2O containing 0.15% NH4OH)

Sources & evidence

ORD record
ord-f5e8645554364cdfaf454390d580647b
Source dataset
uspto-grants-2016_04
Patent number
US09309246B2

Reaction notes

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