Iodine → 2-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile

HRID 549072Notes

Reaction equation

HRID 549072 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[C:13]1([CH3:33])[CH:18]=[CH:17][C:16]([S:19]([N:22]2[C:26]3[N:27]=[CH:28][CH:29]=[C:30]([C:31]#[N:32])[C:25]=3[CH:24]=[CH:23]2)(=[O:21])=[O:20])=[CH:15][CH:14]=1.[I:34]I>O1CCCC1.O>[I:34][C:23]1[N:22]([S:19]([C:16]2[CH:15]=[CH:14][C:13]([CH3:33])=[CH:18][CH:17]=2)(=[O:21])=[O:20])[C:26]2[N:27]=[CH:28][CH:29]=[C:30]([C:31]#[N:32])[C:25]=2[CH:24]=1

Participants

7

Reactant 4

HCID 807IodineHCID 7912DiisopropylamineHCID 224772881H-Pyrrolo[2,3-B]pyridine-4-carbonitrile, 1-[(4-methylphenyl)sulfonyl]-HCID 178418339Butyllithium

Product 1

HCID 224773222-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridine-4-carbonitrileYield 48.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

A stirred solution of diisopropylamine (0.38 mL) in tetrahydrofuran (7 mL), at −70° C. and under nitrogen, was treated with a solution of n-butyllithium in hexanes (1.06 mL, 2.5M) over 5 minutes, whilst maintaining the temperature below −65° C. After stirring for 20 minutes the mixture was added, at −70° C., to a solution of 1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile (0.65 g, Reference Example 63) in tetrahydrofuran (15 mL) and stirred at −70° C. for 45 minutes. A solution of iodine (0.9 g) in tetrahydrofuran (10 mL) was then added at −70° C. The reaction mixture was allowed to warm up to room temperature over 1 hour, and stirred for 18 hours, then treated with water (10 mL). The reaction mixture was evaporated in vacuo and the residue partitioned between ethyl acetate (75 mL) and water (50 mL). The insoluble material was filtered, washed with ether and dried in vacuo to give the title compound (0.45 g) as a white solid. The filtrate was separated and the organics washed sequentially with saturated sodium thiosulfate solution (2×30 mL), water (30 mL) and brine (30 mL), dried over sodium sulfate and evaporated. The residue was triturated with diethyl ether to give a further quantity of the title compound (0.25 g) as a cream solid. TLC RF=0.43 (ethyl acetate/heptane 1:1). MS: 424 (MH+).

Workup

  1. temperaturewhilst maintaining the temperature below −65° C
  2. stirringstirred at −70° C. for 45 minutes
  3. stirringstirred for 18 hours
  4. customThe reaction mixture was evaporated in vacuo
  5. customthe residue partitioned between ethyl acetate (75 mL) and water (50 mL)
  6. filtrationThe insoluble material was filtered
  7. washwashed with ether
  8. customdried in vacuo

Sources & evidence

ORD record
ord-f366e06f6b8c4f13a594f1f7d2a25741
Source dataset
uspto-grants-2011_05
Patent number
US07943616B2

Reaction notes

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