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 887358노트

반응식

HRID 887358 반응식
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

참가 물질

5

반응물 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

생성물 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-carbonitrile수율 9.4%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-ae3f5d0ffeac4ab0830a47e6a8dcc769
출처 데이터셋
uspto-grants-2012_08
특허 번호
US08247421B2

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