Acetic Acid → 5-(4-(piperidin-3-ylmethylamino)-5-(1H-pyrrol-1-yl)pyridin-2-ylamino)pyrazine-2-carbonitrile

HRID 556818Notes

Reaction equation

HRID 556818 reaction equation
[NH2:1][C:2]1[C:3]([NH:17][CH2:18][CH:19]2[CH2:24][CH2:23][CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20]2)=[CH:4][C:5]([NH:8][C:9]2[CH:14]=[N:13][C:12]([C:15]#[N:16])=[CH:11][N:10]=2)=[N:6][CH:7]=1.CO[CH:34]1[CH2:38][CH2:37][CH:36](OC)O1.C(O)(=O)C>ClCCCl.CO>[NH:21]1[CH2:22][CH2:23][CH2:24][CH:19]([CH2:18][NH:17][C:3]2[C:2]([N:1]3[CH:34]=[CH:38][CH:37]=[CH:36]3)=[CH:7][N:6]=[C:5]([NH:8][C:9]3[N:10]=[CH:11][C:12]([C:15]#[N:16])=[N:13][CH:14]=3)[CH:4]=2)[CH2:20]1

Participants

6

Reactant 3

HCID 176Acetic Acid2×HCID 790982,5-DimethoxytetrahydrofuranHCID 66745373Tert-butyl 3-((5-amino-2-(5-cyanopyrazin-2-ylamino)pyridin-4-ylamino)methyl)piperidine-1-carboxylate

Product 1

HCID 596134985-(4-(piperidin-3-ylmethylamino)-5-(1H-pyrrol-1-yl)pyridin-2-ylamino)pyrazine-2-carbonitrileYield 4%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 887MethanolSolvent

Conditions

Temperature
80 °C

Procedure

tert-Butyl 3-((5-amino-2-(5-cyanopyrazin-2-ylamino)pyridin-4-ylamino)methyl)piperidine-1-carboxylate (121 mg, 0.285 mmol) was dissolved in DCE (6 mL) and 2,5-dimethoxytetrahydrofuran (75.3 mg, 0.57 mmol) and acetic acid (2 mL) were added. The solution was heated for 1 h at 80° C. then a further aliquot of acetic acid (2 mL) was added. The solution was heated at 80° C. for a further 30 min then cooled to room temperature and partitioned between dichloromethane and water. The aqueous phase was extracted with dichloromethane and the combined organic phases were evaporated to give an orange oil. The residue was dissolved in methanol and absorbed onto a TsOH solid phase extraction cartridge, washed once with methanol and allowed to stand for 1 h. The cartridge was then eluted with a solution of 7M ammonia in methanol and the solution was evaporated to dryness. The residue was purified by HPLC to give 5-(4-(piperidin-3-ylmethylamino)-5-(1H-pyrrol-1-yl)pyridin-2-ylamino)pyrazine-2-carbonitrile (4.3 mg, 4%).

Workup

  1. temperatureThe solution was heated at 80° C. for a further 30 min
  2. temperaturethen cooled to room temperature
  3. custompartitioned between dichloromethane and water
  4. extractionThe aqueous phase was extracted with dichloromethane
  5. customthe combined organic phases were evaporated
  6. customto give an orange oil
  7. customabsorbed onto a TsOH solid phase extraction cartridge
  8. washwashed once with methanol
  9. washThe cartridge was then eluted with a solution of 7M ammonia in methanol
  10. customthe solution was evaporated to dryness
  11. customThe residue was purified by HPLC

Sources & evidence

ORD record
ord-9b6ad6200140430e871a184e60cbf2df
Source dataset
uspto-grants-2011_11
Patent number
US08058045B2

Reaction notes

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