Triethylamine → 4-Amino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-N-(2,2,2-trifluoroethyl)pyrimidine-5-carboxamide

HRID 510072Notes

Reaction equation

HRID 510072 reaction equation
[NH2:1][C:2]1[C:7]([C:8](O)=[O:9])=[CH:6][N:5]=[C:4]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[CH:17][CH:18]=3)[N:13]([CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[F:27])[N:12]=2)[N:3]=1.C(N(CC)CC)C.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[F:57][C:58]([F:62])([F:61])[CH2:59][NH2:60]>CN(C=O)C.C(#N)C.O>[NH2:1][C:2]1[C:7]([C:8]([NH:60][CH2:59][C:58]([F:62])([F:61])[F:57])=[O:9])=[CH:6][N:5]=[C:4]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[CH:17][CH:18]=3)[N:13]([CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[F:27])[N:12]=2)[N:3]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 9773Ethanamine, 2,2,2-trifluoro-HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66614346HCID 66614346, compound

Product 1

HCID 666142844-Amino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-N-(2,2,2-trifluoroethyl)pyrimidine-5-carboxamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

300 mg (0.82 mmol) of 4-amino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidine-5-carboxylic acid (example 102A), 0.230 ml (1.65 mmol) of triethylamine and 139 mg (0.91 mmol) of 1-hydroxyl-1H-benzotriazole were dissolved in 2.2 ml of DMF, and 174 mg (0.91 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were added. While cooling with ice, 70 μl (90 mg, 0.91 mmol) of 2,2,2-trifluoroethylamine were added, and the mixture was reacted at room temperature overnight. The mixture was brought into solution with 4 ml of acetonitrile/water and purified by means of preparative HPLC [column: Reprosil C18, 10 μm, 250*40 mm; eluent: acetonitrile/0.05% formic acid; gradient: 15% acetonitrile→95% acetonitrile]. Thus, 110 mg (28% of theory) of the target compound were obtained.

Workup

  1. additionwere added
  2. customthe mixture was reacted at room temperature overnight
  3. custompurified by means of preparative HPLC [column: Reprosil C18, 10 μm, 250*40 mm; eluent: acetonitrile/0.05% formic acid; gradient: 15% acetonitrile→95% acetonitrile]
  4. customThus, 110 mg (28% of theory) of the target compound were obtained

Sources & evidence

ORD record
ord-af2e1a19ebd84ae7a84570e2b92eebeb
Source dataset
uspto-grants-2015_08
Patent number
US09096592B2

Reaction notes

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