Diisopropylethylamine → (S)-N-(1-(5-Fluoropyridin-2-yl)ethyl)-2-(pyrazolo[1,5-a]pyrazin-3-yl)pyrimidin-4-amine

HRID 1500778Notes

Reaction equation

HRID 1500778 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]2[CH:9]=[N:10][N:11]3[CH:16]=[CH:15][N:14]=[CH:13][C:12]=23)[N:3]=1.[F:17][C:18]1[CH:19]=[CH:20][C:21]([C@@H:24]([NH2:26])[CH3:25])=[N:22][CH:23]=1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[F:17][C:18]1[CH:19]=[CH:20][C:21]([C@@H:24]([NH:26][C:2]2[CH:7]=[CH:6][N:5]=[C:4]([C:8]3[CH:9]=[N:10][N:11]4[CH:16]=[CH:15][N:14]=[CH:13][C:12]=34)[N:3]=2)[CH3:25])=[N:22][CH:23]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 16097531(S)-1-(5-Fluoropyridin-2-yl)ethanamineHCID 86691785HCID 86691785, compound

Product 1

HCID 53375187(S)-N-(1-(5-Fluoropyridin-2-yl)ethyl)-2-(pyrazolo[1,5-a]pyrazin-3-yl)pyrimidin-4-amineYield 4.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 3-(4-chloropyrimidin-2-yl)pyrazolo[1,5-a]pyrazine (Preparation 31, 170 mg, 0.61 mmol), (S)-1-(5-fluoropyridin-2-yl)ethanamine (85 mg, 0.61 mmol, prepared as described in WO2006/82392A1) and diisopropylethylamine (122 μL, 0.70 mmol) in N,N′-dimethylformamide (5 mL) was heated to 150° C. in a microwave oven for 75 min. The solvent was then removed under reduced pressure and the residue was partitioned between 4% aqueous sodium hydrogen carbonate solution and ethyl acetate. The organic phase was separated, washed with brine, dried (MgSO4) and concentrated to give a crude which was purified by reverse phase chromatography (C-18 silica from Waters, water/acetonitrile/methanol as eluents [0.1% v/v formic acid buffered] 5% to 50%) to give the title compound (9 mg, 4%) as an oil. The corresponding fumarate salt was prepared by adding a solution of fumaric acid (3.1 mg, 0.027 mmol) in ethanol (0.5 mL) to a solution of the title compound (as free base, 9 mg, 0.027 mmol) in ethanol (2 mL) followed by evaporation of the solvent. The resulting solid was dried in an oven under vacuum to give 11 mg of the desired fumarate salt.

Workup

  1. customThe solvent was then removed under reduced pressure
  2. customthe residue was partitioned between 4% aqueous sodium hydrogen carbonate solution and ethyl acetate
  3. customThe organic phase was separated
  4. washwashed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customto give a crude which
  8. customwas purified by reverse phase chromatography (C-18 silica from Waters, water/acetonitrile/methanol as eluents [0.1% v/v formic acid

Sources & evidence

ORD record
ord-1699b4c4c1854f76837e6bed2c6f131c
Source dataset
uspto-grants-2015_12
Patent number
US09206183B2

Reaction notes

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