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

HRID 384662Notes

Reaction equation

HRID 384662 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.[BH4-].[Na+].[CH3:34][OH:35]>>[OH:35][CH2:34][C:2]1[CH:3]=[CH:4][N:1]([C:2]2[C:3]([NH:17][CH2:18][CH:19]3[CH2:24][CH2:23][CH2:22][NH:21][CH2:20]3)=[CH:4][C:5]([NH:8][C:9]3[N:10]=[CH:11][C:12]([C:15]#[N:16])=[N:13][CH:14]=3)=[N:6][CH:7]=2)[CH:7]=1

Participants

4

Reactant 3

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 66745373Tert-butyl 3-((5-amino-2-(5-cyanopyrazin-2-ylamino)pyridin-4-ylamino)methyl)piperidine-1-carboxylate

Product 1

HCID 596133825-(5-(3-(hydroxymethyl)-1H-pyrrol-1-yl)-4-(piperidin-3-ylmethylamino)pyridin-2-ylamino)pyrazine-2-carbonitrileYield 11%

Conditions

Temperature
0 °C

Procedure

tert-Butyl 3-((5-amino-2-(5-cyanopyrazin-2-ylamino)pyridin-4-ylamino)methyl)piperidine-1-carboxylate (37 mg, 0.074 mmol) (Synthesis 107-A) was dissolved in methanol (1.5 mL) and cooled to 0° C. Sodium borohydride (15 mg, 0.396 mmol) was added and the reaction was stirred at 0° C. for 4 h. The solution was evaporated and the residue was partitioned between water and dichloromethane. The two phases were separated and the aqueous phase was extracted with dichloromethane. The combined organic phases were evaporated and the residue was dissolved in methanol (1 mL) and absorbed onto a TsOH solid phase extraction cartridge. After 1.5 h the cartridge was eluted with 7M ammonia in methanol. The basic eluent was evaporated to dryness. The residue was purified by HPLC to give 5-(5-(3-(hydroxymethyl)-1H-pyrrol-1-yl)-4-(piperidin-3-ylmethylamino)pyridin-2-ylamino)pyrazine-2-carbonitrile (3.18 mg, 11%).

Workup

  1. customThe solution was evaporated
  2. customthe residue was partitioned between water and dichloromethane
  3. customThe two phases were separated
  4. extractionthe aqueous phase was extracted with dichloromethane
  5. customThe combined organic phases were evaporated
  6. dissolutionthe residue was dissolved in methanol (1 mL)
  7. customabsorbed onto a TsOH solid phase extraction cartridge
  8. washAfter 1.5 h the cartridge was eluted with 7M ammonia in methanol
  9. customThe basic eluent was evaporated to dryness
  10. customThe residue was purified by HPLC

Sources & evidence

ORD record
ord-2f4128242c774c44a1824611ee30ec00
Source dataset
uspto-grants-2013_02
Patent number
US08367658B2

Reaction notes

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