Sodium Hydroxide → 4-[4-[5-Amino-6-[3-[4-(methylaminomethyl)phenyl]isoxazol-5-yl]pyrazin-2-yl]-2-pyridyl]tetrahydropyran-4-carboxamide

HRID 331501Notes

Reaction equation

HRID 331501 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:22]2[CH:27]=[CH:26][N:25]=[C:24]([C:28]3([C:34]#[N:35])[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[CH:23]=2)=[N:6][C:7]=1[C:8]1[O:12][N:11]=[C:10]([C:13]2[CH:18]=[CH:17][C:16]([CH2:19][NH:20][CH3:21])=[CH:15][CH:14]=2)[CH:9]=1.[OH-:36].[Na+]>CO.O>[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:22]2[CH:27]=[CH:26][N:25]=[C:24]([C:28]3([C:34]([NH2:35])=[O:36])[CH2:29][CH2:30][O:31][CH2:32][CH2:33]3)[CH:23]=2)=[N:6][C:7]=1[C:8]1[O:12][N:11]=[C:10]([C:13]2[CH:18]=[CH:17][C:16]([CH2:19][NH:20][CH3:21])=[CH:15][CH:14]=2)[CH:9]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 708186554-[4-[5-Amino-6-[3-[4-(methylaminomethyl)phenyl]isoxazol-5-yl]pyrazin-2-yl]-2-pyridyl]tetrahydropyran-4-carbonitrile

Product 1

HCID 708191034-[4-[5-Amino-6-[3-[4-(methylaminomethyl)phenyl]isoxazol-5-yl]pyrazin-2-yl]-2-pyridyl]tetrahydropyran-4-carboxamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

4-[4-[5-amino-6-[3-[4-(methylaminomethyl)phenyl]isoxazol-5-yl]pyrazin-2-yl]-2-pyridyl]tetrahydropyran-4-carbonitrile (Trifluoroacetic Acid (1)) (18 mg, 0.03002 mmol) was dissolved in methanol (1 mL) and then 1 M sodium hydroxide solution (300.2 μL of 1 M, 0.3002 mmol) was added. The reaction mixture was heated in the microwave to 100° C. for 45 minutes. The reaction mixture was diluted with water and extracted with ethyl acetate. The extracted organic layer was dried over MgSO4, filtered and concentrated in vacuo to a solid. Compound was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 mM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% trifluoroacetic acid in water; solvent B: acetonitrile) over 16 minutes at 25 mL/minutes], combined fractions were then freeze-dried to give 4-[4-[5-amino-6-[3-[4-(methylaminomethyl)phenyl]isoxazol-5-yl]pyrazin-2-yl]-2-pyridyl]tetrahydropyran-4-carboxamide Compound I-13 as a yellow solid (6 mg, 31.37%). 1H NMR (400.0 MHz, DMSO-d6) δ 2.2-2.25 (m, 2H), 2.45-2.5 (m, 2H), 2.65-2.7 (m, 3H), 3.6-3.75 (m, 4H), 4.28-4.33 (m, 2H), 7.18-7.2 (m, 1H), 7.27-7.3 (m, 1H), 7.35-7.39 (m, 1H), 7.7 (d, 2H), 7.85 (s, 1H), 8.05 (d, 1H), 8.1 (s, 1H), 8.18 (d, 2H), 8.7 (d, 1H), 8.88 (br s, 2H), 9.05 (s, 1H); LC/MS m/z 486.2 [M+H]+.

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe extracted organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo to a solid
  5. customCompound was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 mM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% trifluoroacetic acid in water; solvent B: acetonitrile) over 16 minutes at 25 mL/minutes]
  6. customwere then freeze-dried

Sources & evidence

ORD record
ord-1919bd68015a4a32a0ae2336b5681b8c
Source dataset
uspto-grants-2014_11
Patent number
US08877759B2

Reaction notes

Loading…