Dichloromethane → 5-[7-(1-methyl-cyclohexanecarbonyl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-thiophene-2-carboxylic acid

HRID 547482Notes

Reaction equation

HRID 547482 reaction equation
OB(O)[C:3]1[S:7][C:6]([C:8]([OH:10])=[O:9])=[CH:5][CH:4]=1.Br[C:13]1[N:14]=[C:15]2[C:21]([C:22]([C:24]3([CH3:30])[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]3)=[O:23])=[CH:20][N:19]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[C:16]2=[N:17][CH:18]=1.C(=O)([O-])[O-].[K+].[K+].C(Cl)Cl>O1CCOCC1.O.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]>[CH3:30][C:24]1([C:22]([C:21]2[C:15]3[C:16](=[N:17][CH:18]=[C:13]([C:3]4[S:7][C:6]([C:8]([OH:10])=[O:9])=[CH:5][CH:4]=4)[N:14]=3)[N:19]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:36])([CH3:38])[CH3:37])[CH:20]=2)=[O:23])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 27798075-Boronothiophene-2-carboxylic acidHCID 57829583[2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-(1-methyl-cyclohexyl)-methanone

Product 1

HCID 578295975-[7-(1-methyl-cyclohexanecarbonyl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-thiophene-2-carboxylic acidYield 50.6%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 5-(dihydroxyboryl)-2-thiophene-carboxylic acid (1.0 g, 5.4 mmol), [2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-(1-methyl-cyclohexyl)-methanone (2.2 g, 4.9 mmol), potassium carbonate (2.0 g, 15 mmol), and Pd(dppf)Cl2.CH2Cl2 (0.400 g, 0.489 mmol) in 12 mL of 1,4-dioxane and 3 mL of water was stirred at 120° C. in a microwave for 40 min. The resulting red suspension was partitioned between 60 mL of ethyl acetate and 100 mL of water, and the aqueous layer was extracted with three 60 mL portions of ethyl acetate. The combined organic layers were dried over MgSO4, filtered and concentrated to a residue. Column chromatography (0->50% EtOAc/hexanes) afforded 1.24 g (46%) of 5-[7-(1-methyl-cyclohexanecarbonyl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-thiophene-2-carboxylic acid as a brown solid.

Workup

  1. customThe resulting red suspension was partitioned between 60 mL of ethyl acetate and 100 mL of water
  2. extractionthe aqueous layer was extracted with three 60 mL portions of ethyl acetate
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated to a residue

Sources & evidence

ORD record
ord-e2c4f2cf268a4717a933f22b82635a9a
Source dataset
uspto-grants-2011_05
Patent number
US07939531B2

Reaction notes

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