Lithium Hydroxide → 2-(1-(6-(4-hydroxy-1-methylpiperidin-4-yl)pyridin-3-yl)ethylamino)-4-(5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidine-5-carbonitrile

HRID 40856Notes

Reaction equation

HRID 40856 reaction equation
CS([C:5]1[N:10]=[C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17]([C:20]([F:23])([F:22])[F:21])[CH:18]=3)[N:13](S(C3C=CC(C)=CC=3)(=O)=O)[CH:12]=2)[C:8]([C:34]#[N:35])=[CH:7][N:6]=1)(=O)=O.[NH2:36][CH:37]([C:39]1[CH:40]=[CH:41][C:42]([C:45]2([OH:52])[CH2:50][CH2:49][N:48]([CH3:51])[CH2:47][CH2:46]2)=[N:43][CH:44]=1)[CH3:38].[OH-].[Li+]>O1CCCC1>[OH:52][C:45]1([C:42]2[N:43]=[CH:44][C:39]([CH:37]([NH:36][C:5]3[N:10]=[C:9]([C:11]4[C:19]5[C:14](=[N:15][CH:16]=[C:17]([C:20]([F:21])([F:22])[F:23])[CH:18]=5)[NH:13][CH:12]=4)[C:8]([C:34]#[N:35])=[CH:7][N:6]=3)[CH3:38])=[CH:40][CH:41]=2)[CH2:50][CH2:49][N:48]([CH3:51])[CH2:47][CH2:46]1

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 574658474-(5-(1-Aminoethyl)pyridin-2-yl)-1-methylpiperidin-4-olHCID 594143252-Methylsulfonyl-4-[1-(p-tolylsulfonyl)-5-(trifluoromethyl)-pyrrolo[5,4-b]pyridin-3-yl]pyrimidine-5-carbonitrile

Product 1

HCID 574658452-(1-(6-(4-hydroxy-1-methylpiperidin-4-yl)pyridin-3-yl)ethylamino)-4-(5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidine-5-carbonitrileYield 9.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-(Methylsulfonyl)-4-(1-tosyl-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidine-5-carbonitrile (160.2 mg, 0.255 mmol) was added to a solution of 4-(5-(1-aminoethyl)pyridin-2-yl)-1-methylpiperidin-4-ol (66.01 mg, 0.28 mmol) in tetrahydrofuran (8 mL). The reaction mixture was stirred under nitrogen at room temperature for 18 hours. 1M Lithium hydroxide (1.020 mL of 1 M, 1.020 mmol) was added and the reaction mixture was stirred at room temperature for 4 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 (12.5 mg, 9% yield).

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 4 hours
  2. customThe crude mixture was partitioned between ethyl acetate and brine
  3. dry with materialThe organic extracts were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. 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]
  7. customThe fractions were collected
  8. customfreeze-dried

Sources & evidence

ORD record
ord-ad4909c82ba946f9bd78fef667d46595
Source dataset
uspto-grants-2013_09
Patent number
US08530489B2

Reaction notes

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