Iodine → 7-Iodo-1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridine

HRID 1627990Notes

Reaction equation

HRID 1627990 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[CH3:13][N:14]1[C:18]2=[C:19]3[CH:25]=[CH:24][N:23]([S:26]([C:29]4[CH:35]=[CH:34][C:32]([CH3:33])=[CH:31][CH:30]=4)(=[O:28])=[O:27])[C:20]3=[N:21][CH:22]=[C:17]2[CH:16]=[N:15]1.[I:36]I>C1COCC1.O>[I:36][C:24]1[N:23]([S:26]([C:29]2[CH:35]=[CH:34][C:32]([CH3:33])=[CH:31][CH:30]=2)(=[O:27])=[O:28])[C:20]2=[N:21][CH:22]=[C:17]3[CH:16]=[N:15][N:14]([CH3:13])[C:18]3=[C:19]2[CH:25]=1

Participants

7

Reactant 4

HCID 807IodineHCID 7912DiisopropylamineHCID 580098301-Methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridineHCID 178418339Butyllithium

Product 1

HCID 580099867-Iodo-1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridineYield 30.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-74 °C

Procedure

Diisopropylamine (4.32 mL, 30.6 mmol) in THF (20 mL) was cooled to −74° C. n-BuLi (1.6 M in cyclohexane, 21.04 mL, 33.7 mmol) was added drop-wise over 15 min. After about 20 min, the mixture was added to 1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridine (5.0 g, 15 mmol) in THF (100 mL) at about −74° C. over about 10 min. After about 1 h, a solution of iodine (4.51 g, 17.7 mmol) in THF (30 mL) was added over about 20 min. The mixture was stirred at about −74° C. for about 3 h and then allowed to warm to rt and stirred overnight. To the mixture was added water (80 mL) and the mixture was extracted with EtOAc (3×100 mL). The organic layers were combined, dried over anhydrous MgSO4 and concentrated under reduced pressure. The residue was purified by flash chromatography with a gradient of 0 to 80% EtOAc/heptane to give 7-iodo-1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridine (2.08 g, 30%): LC/MS (Table 2, Method a) Rt=2.44 min; MS m/z 453 (M+H)+.

Workup

  1. additionwas added drop-wise over 15 min
  2. waitAfter about 1 h
  3. temperatureto warm to rt
  4. stirringstirred overnight
  5. extractionthe mixture was extracted with EtOAc (3×100 mL)
  6. dry with materialdried over anhydrous MgSO4
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by flash chromatography with a gradient of 0 to 80% EtOAc/heptane

Sources & evidence

ORD record
ord-8548d1c5d89a47a6a040823bfe71629d
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

Loading…