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 887358Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 887358
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

Komponenten

5

Edukt 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

Produkt 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-carbonitrileAusbeute 9,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-ae3f5d0ffeac4ab0830a47e6a8dcc769
Quelldatensatz
uspto-grants-2012_08
Patentnummer
US08247421B2

Notizen zur Reaktion

Wird geladen…