Thiophenol → 2-(phenylthio)-4-(5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidine-5-carbonitrile

HRID 1853485Notes

Reaction equation

HRID 1853485 reaction equation
C[S:2]([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.[C:36]1(S)[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.CCN(C(C)C)C(C)C.O[Li].O>C1COCC1.O>[C:36]1([S:2][C:5]2[N:10]=[C:9]([C:11]3[C:19]4[C:14](=[N:15][CH:16]=[C:17]([C:20]([F:23])([F:22])[F:21])[CH:18]=4)[NH:13][CH:12]=3)[C:8]([C:34]#[N:35])=[CH:7][N:6]=2)[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

Participants

7

Reactant 4

HCID 7969ThiophenolHCID 81531DiisopropylethylamineHCID 168937Lithium hydroxide, monohydrateHCID 594143252-Methylsulfonyl-4-[1-(p-tolylsulfonyl)-5-(trifluoromethyl)-pyrrolo[5,4-b]pyridin-3-yl]pyrimidine-5-carbonitrile

Product 1

HCID 574716552-(phenylthio)-4-(5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidine-5-carbonitrileYield 47%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

2-(methylsulfonyl)-4-(1-tosyl-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidine-5-carbonitrile (75 mg, 0.15 mmol) was heated with benzenethiol (31 uL, 0.30 mmol, 2.0 Eq.) and DIPEA (78 uL, 0.45 mmol, 3.0 Eq.) in THF (2 mL) under microwave conditions at 100° C. for 10 minutes. A solution of LiOH.H2O (32 mg, 0.75 mmol, 5.0 Eq.) in water (1 mL) was added to the mixture and the reaction left to stir for 90 minutes. The reaction was partitioned between EtOAc and water and the aqueous phase extracted with EtOAc. The combined organic layers were dried (Na2SO4) and concentrated in vacuo. The resultant solid was purified by column chromatography (ISCO Companion™, 12 g column, 0-30% EtOAc/Petroleum Ether) and lyophilized to give the title compound as a pale yellow solid (28 mg, 47% over 2 steps).

Workup

  1. waitthe reaction left
  2. customThe reaction was partitioned between EtOAc and water
  3. extractionthe aqueous phase extracted with EtOAc
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe resultant solid was purified by column chromatography (ISCO Companion™, 12 g column, 0-30% EtOAc/Petroleum Ether)

Sources & evidence

ORD record
ord-0f3cf166e89f472ba452329a862f05eb
Source dataset
uspto-grants-2015_02
Patent number
US08962642B2

Reaction notes

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