Lithium Hydroxide → HCID 178462367, compound

HRID 1853480Notes

Reaction equation

HRID 1853480 reaction equation
[NH2:1][C@@H:2]([C@H:4]1[CH2:9][CH2:8][C@H:7]([NH:10][C:11](=[O:15])[C@H:12]([OH:14])[CH3:13])[CH2:6][CH2:5]1)[CH3:3].CN(C=O)C.[F:21][C:22]([F:55])([F:54])[C:23]1[CH:24]=[C:25]2[C:31]([C:32]3[C:37]([C:38]#[N:39])=[CH:36][N:35]=[C:34](S(C)(=O)=O)[N:33]=3)=[CH:30][N:29](S(C3C=CC(C)=CC=3)(=O)=O)[C:26]2=[N:27][CH:28]=1.[OH-].[Li+]>C1COCC1>[C:38]([C:37]1[C:32]([C:31]2[C:25]3[C:26](=[N:27][CH:28]=[C:23]([C:22]([F:54])([F:21])[F:55])[CH:24]=3)[NH:29][CH:30]=2)=[N:33][C:34]([NH:1][C@@H:2]([C@H:4]2[CH2:5][CH2:6][C@H:7]([NH:10][C:11](=[O:15])[C@H:12]([OH:14])[CH3:13])[CH2:8][CH2:9]2)[CH3:3])=[N:35][CH:36]=1)#[N:39]

Participants

6

Reactant 4

HCID 3939Lithium HydroxideHCID 6228DimethylformamideHCID 594143252-Methylsulfonyl-4-[1-(p-tolylsulfonyl)-5-(trifluoromethyl)-pyrrolo[5,4-b]pyridin-3-yl]pyrimidine-5-carbonitrileHCID 178462368HCID 178462368, compound

Product 1

HCID 178462367HCID 178462367, compoundYield 18%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Trans-(R)—N-(4-((R)-1-aminoethyl)cyclohexyl)-2-hydroxypropanamide (45 mg, 0.21 mmol) was dissolved in THF (6 mL) and DMF (2 mL) and stirred over 4 Å molecular sieves for 10 minutes. 4-(5-(trifluoromethyl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(methylsulfonyl)pyrimidine-5-carbonitrile (131.9 mg, 0.2100 mmol) was added. The reaction mixture was stirred under nitrogen at ambient temperature for 18 hours. The molecular sieves was removed by filtration and washed with EtOAc. The filtrate was washed with water, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue dissolved in tetrahydrofuran (6 mL). Lithium hydroxide (840.0 μL of 1 M, 0.8400 mmol) was added and the reaction mixture was stirred at room temperature for 18 hours. The crude mixture was partitioned between ethyl acetate and brine. The organic extracts were dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected, passed through a sodium bicarbonate cartridge and freeze-dried to give the title compound as a white solid (19 mg, 18% yield).

Workup

  1. customThe molecular sieves was removed by filtration
  2. washwashed with EtOAc
  3. washThe filtrate was washed with water
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue dissolved in tetrahydrofuran (6 mL)
  8. stirringthe reaction mixture was stirred at room temperature for 18 hours
  9. customThe crude mixture was partitioned between ethyl acetate and brine
  10. dry with materialThe organic extracts were dried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]
  14. customThe fractions were collected
  15. customfreeze-dried

Sources & evidence

ORD record
ord-9340e79d99c64e30a3ed0dcc901cc88e
Source dataset
uspto-grants-2015_02
Patent number
US08962642B2

Reaction notes

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