Water → 7-(6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-3-yl)-1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridine

HRID 1628007Notes

Reaction equation

HRID 1628007 reaction equation
Br[C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][C:5]2=[N:4][CH:3]=1.C([Mg]Br)(C)C.I[C:16]1[N:28]([S:29]([C:32]2[CH:38]=[CH:37][C:35]([CH3:36])=[CH:34][CH:33]=2)(=[O:31])=[O:30])[C:19]2=[N:20][CH:21]=[C:22]3[CH:26]=[N:25][N:24]([CH3:27])[C:23]3=[C:18]2[CH:17]=1.O>C1COCC1.CN(C=O)C.[Cl-].[Zn+2].[Cl-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:4]1[CH:3]=[C:2]([C:16]2[N:28]([S:29]([C:32]3[CH:38]=[CH:37][C:35]([CH3:36])=[CH:34][CH:33]=3)(=[O:31])=[O:30])[C:19]3=[N:20][CH:21]=[C:22]4[CH:26]=[N:25][N:24]([CH3:27])[C:23]4=[C:18]3[CH:17]=2)[N:6]2[CH2:7][CH2:8][CH2:9][C:5]=12

Participants

9

Reactant 4

HCID 962WaterHCID 269673883-bromo-5H,6H,7H-pyrrolo[1,2-a]imidazoleHCID 580099867-Iodo-1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridineHCID 178418365HCID 178418365, compound

Product 1

HCID 583824237-(6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-3-yl)-1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridineYield 241.7%

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-30 °C

Procedure

To a flask was added 3-bromo-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole (0.250 g, 1.33 mmol, Apollo) and THF (3 mL). The mixture was cooled to about −30° C. and then i-PrMgBr (2.0 M in THF, 0.735 mL, 1.47 mmol) was added. After about 15 min, in a separate flask, zinc chloride (0.219 g, 1.604 mmol) was dissolved in THF (3 mL) and then the solution was added dropwise to the mixture. After about 30 min at about −20° C., 7-iodo-1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridine (0.250 g, 0.553 mmol; Preparation #1) and Pd(Ph3P)4 (0.093 g, 0.080 mmol), dissolved in DMF (2 mL) were then added to the mixture and it was then heated to about 80° C. for about 90 min. Water was added (30 mL) and solids were collected by filtration and dried under reduced pressure to provide 7-(6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-3-yl)-1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridine (0.578 g, 100%): LC/MS (Table 2, Method c) Rt=1.27 min; MS m/z 433 (M+H)+.

Workup

  1. additionthe solution was added dropwise to the mixture
  2. waitAfter about 30 min at about −20° C.
  3. additionwere then added to the mixture and it
  4. temperaturewas then heated to about 80° C. for about 90 min
  5. filtrationwere collected by filtration
  6. customdried under reduced pressure

Sources & evidence

ORD record
ord-f223af7a3ffe4a8595bd6faefdab410f
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

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