1,2-Diiodoethane → 2-Amino-6-({[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methyl}sulfanyl)-4-(2-iodo-1,3-thiazol-5-yl)pyridine-3,5-dicarbonitrile

HRID 1969478Notes

Reaction equation

HRID 1969478 reaction equation
[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:10]2[S:14][CH:13]=[N:12][CH:11]=2)[C:5]([C:15]#[N:16])=[C:4]([S:17][CH2:18][C:19]2[N:20]=[C:21]([C:24]3[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=3)[S:22][CH:23]=2)[N:3]=1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[I:41]CCI>C1COCC1>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:10]2[S:14][C:13]([I:41])=[N:12][CH:11]=2)[C:5]([C:15]#[N:16])=[C:4]([S:17][CH2:18][C:19]2[N:20]=[C:21]([C:24]3[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=3)[S:22][CH:23]=2)[N:3]=1

Participants

5

Reactant 3

HCID 122241,2-DiiodoethaneHCID 2733832Lithium HexamethyldisilazideHCID 442296432-Amino-6-([2-(4-chlorophenyl)-1,3-thiazol-4-yl]methylsulfanyl)-4-(1,3-thiazol-5-yl)pyridine-3,5-dicarbonitrile

Product 1

HCID 668967562-Amino-6-({[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methyl}sulfanyl)-4-(2-iodo-1,3-thiazol-5-yl)pyridine-3,5-dicarbonitrileYield 15%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Under argon, 230 mg (0.493 mmol) of 2-amino-6-({[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methyl}sulfanyl)-4-(1,3-thiazol-5-yl)pyridine-3,5-dicarbonitrile were dissolved in 15 ml of THF and cooled to −78° C. At this temperature, 1.182 ml (1.182 mmol) of lithium 1,1,1,3,3,3-hexamethyldisilazan-2-ide (1 M in THF) were added dropwise. After 1 h of stirring at −78° C., a solution of 0.143 ml (1.084 mmol) of 1,2-diiodethane in 5 ml of THF was added dropwise, and the reaction mixture was stirred at −78° C. for a further hour. The reaction was terminated by addition of 20 ml of 10% strength aqueous sodium thiosulfate solution. After the mixture had warmed to room temperature, the aqueous phase was extracted three times with dichloromethane. The combined organic phases were dried over sodium sulfate, filtered and concentrated. The residue was purified by preparative HPLC (mobile phase A=water, B=acetonitrile; gradient: 0.0 min 10% B, 30 min 95% B, 34 min 95% B, 34.01 min 10% B, 38 min 10% B; flow rate: 50 ml/min; +0.1% TFA). The solid which had precipitated from the acetonitrile/water mixture was filtered off and dried under high vacuum. This gave 60 mg of the target compound in a purity of 76% (yield: 15% of theory).

Workup

  1. stirringthe reaction mixture was stirred at −78° C. for a further hour
  2. customThe reaction was terminated by addition of 20 ml of 10% strength aqueous sodium thiosulfate solution
  3. temperatureAfter the mixture had warmed to room temperature
  4. extractionthe aqueous phase was extracted three times with dichloromethane
  5. dry with materialThe combined organic phases were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by preparative HPLC (mobile phase A=water, B=acetonitrile; gradient: 0.0 min 10% B, 30 min 95% B, 34 min 95% B, 34.01 min 10% B, 38 min 10% B; flow rate: 50 ml/min; +0.1% TFA)
  9. customThe solid which had precipitated from the acetonitrile/water mixture
  10. filtrationwas filtered off
  11. customdried under high vacuum

Sources & evidence

ORD record
ord-6fc72b0cf2ce4ff8a2ad7befd1d65f39
Source dataset
uspto-grants-2013_04
Patent number
US08426602B2

Reaction notes

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