Trifluoroacetic acid → 2-amino-N-(4-(4-aminopiperidin-1-yl)pyridin-3-yl)-6-(cyanomethyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide

HRID 524843Notes

Reaction equation

HRID 524843 reaction equation
[NH2:1][C:2]1[C:13]([C:14]([NH:16][C:17]2[CH:18]=[N:19][CH:20]=[CH:21][C:22]=2[N:23]2[CH2:28][CH2:27][CH:26]([NH:29]C(=O)OC(C)(C)C)[CH2:25][CH2:24]2)=[O:15])=[C:5]2[N:6]=[CH:7][C:8]([CH2:10][C:11]#[N:12])=[CH:9][N:4]2[N:3]=1.NC1C(C(ON2C3C=CC=CC=3N=N2)=O)=C2N=CC(CC#N)=CN2N=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:1][C:2]1[C:13]([C:14]([NH:16][C:17]2[CH:18]=[N:19][CH:20]=[CH:21][C:22]=2[N:23]2[CH2:24][CH2:25][CH:26]([NH2:29])[CH2:27][CH2:28]2)=[O:15])=[C:5]2[N:6]=[CH:7][C:8]([CH2:10][C:11]#[N:12])=[CH:9][N:4]2[N:3]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 86720897tert-butyl N-[1-[3-[[2-amino-6-(cyanomethyl)pyrazolo[1,5-a]pyrimidine-3-carbonyl]amino]-4-pyridyl]-4-piperidyl]carbamateHCID 901998921H-benzo[d][1,2,3]triazol-1-yl 2-amino-6-(cyanomethyl)pyrazolo[1,5-a]pyrimidine-3-carboxylate

Product 1

HCID 867208962-amino-N-(4-(4-aminopiperidin-1-yl)pyridin-3-yl)-6-(cyanomethyl)pyrazolo[1,5-a]pyrimidine-3-carboxamideYield 31%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl N-[1-[3-[[2-amino-6-(cyanomethyl)pyrazolo[1,5-a]pyrimidine-3-carbonyl]amino]-4-pyridyl]-4-piperidyl]carbamate prepared according to a method similar to the one described in Example 1 (70 mg, 0.1424 mmol) in DCM (4 mL) was added TFA (1 mL, 12.98 mmol) and the mixture was stirred at ambient temperature for 1.5 hours. The reaction mixture was evaporated to dryness and purified by HPLC: 10-90% ACN in Water (TFA modifier) and the fractions were freeze-dried. The solid residue was dissolved in methanol (1 mL) and loaded onto a pre-wetted (15 mL methanol) 2 g SCX-2 cartridge. The cartridge was washed with methanol (2×15 mL) then the product eluted as a free base using 2M ammonia in methanol solution (3×15 mL). The product-containing fractions were evaporated to dryness, re-dissolved in water/methanol and freeze-dried to afford the desired product as a yellow solid (17 mg, 31%). MS (ES+) 391.1.

Workup

  1. customThe reaction mixture was evaporated to dryness
  2. custompurified by HPLC
  3. dry with material10-90% ACN in Water (TFA modifier) and the fractions were freeze-dried
  4. dissolutionThe solid residue was dissolved in methanol (1 mL)
  5. washThe cartridge was washed with methanol (2×15 mL)
  6. washthe product eluted as a free base
  7. customThe product-containing fractions were evaporated to dryness
  8. dissolutionre-dissolved in water/methanol
  9. customfreeze-dried

Sources & evidence

ORD record
ord-6f3fb9681738459bbc499dc71008bd43
Source dataset
uspto-grants-2016_05
Patent number
US09340546B2

Reaction notes

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