Potassium Carbonate → Benzyl 3-(5-cyano-2-(methylthio)pyrimidin-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-ylcarbamate

HRID 40864Notes

Reaction equation

HRID 40864 reaction equation
CC1(C)C(C)(C)OB([C:9]2[C:17]3[C:12](=[N:13][CH:14]=[C:15]([NH:18][C:19](=[O:28])[O:20][CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[CH:16]=3)[N:11]([S:29]([C:32]3[CH:38]=[CH:37][C:35]([CH3:36])=[CH:34][CH:33]=3)(=[O:31])=[O:30])[CH:10]=2)O1.Cl[C:41]1[C:46]([C:47]#[N:48])=[CH:45][N:44]=[C:43]([S:49][CH3:50])[N:42]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:47]([C:46]1[C:41]([C:9]2[C:17]3[C:12](=[N:13][CH:14]=[C:15]([NH:18][C:19](=[O:28])[O:20][CH2:21][C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=4)[CH:16]=3)[N:11]([S:29]([C:32]3[CH:38]=[CH:37][C:35]([CH3:36])=[CH:34][CH:33]=3)(=[O:30])=[O:31])[CH:10]=2)=[N:42][C:43]([S:49][CH3:50])=[N:44][CH:45]=1)#[N:48]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 131141834-Chloro-2-(methylsulfanyl)pyrimidine-5-carbonitrileHCID 59414528Benzyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-ylcarbamate

Product 1

HCID 68668331Benzyl 3-(5-cyano-2-(methylthio)pyrimidin-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-ylcarbamateYield 42.2%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 21863594Toluene ethanolSolvent

Conditions

Temperature
100 °C

Procedure

Benzyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-ylcarbamate (0.50 g, 0.91 mmol) in toluene/ethanol (7.5 mL:2.0 mL) was treated with 4-chloro-2-(methylthio)pyrimidine-5-carbonitrile (0.186 g, 1.00 mmol, 1.1 Eq) and 2M aqueous potassium carbonate (1.37 mL, 2.74 mmol, 3.0 Eq), degassed and stirred under nitrogen for 20 minutes. Pd(dppf)2Cl2 (0.075 g, 0.1 Eq) was added and the mixture allowed to heat at 100° C. for 1.5 hours. The reaction was partitioned between EtOAc and saturated aqueous sodium carbonate and the organic layer separated, dried over magnesium sulphate and evaporated to dryness. The mixture was purified by column chromatography eluting with 10% EtOAc/Petroleum ether to yield a white solid (0.219 g, 42%).

Workup

  1. customdegassed
  2. customThe reaction was partitioned between EtOAc and saturated aqueous sodium carbonate
  3. customthe organic layer separated
  4. dry with materialdried over magnesium sulphate
  5. customevaporated to dryness
  6. customThe mixture was purified by column chromatography
  7. washeluting with 10% EtOAc/Petroleum ether

Sources & evidence

ORD record
ord-778fecfc56b8447383346e117a1a288a
Source dataset
uspto-grants-2013_09
Patent number
US08530489B2

Reaction notes

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