Iodine → HCID 67006515, compound

HRID 563353Notes

Reaction equation

HRID 563353 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.II.C(N(CC)CC)C.[Si:29]([O:36][CH2:37][CH2:38][C@@H:39]([NH:54][C:55]1[CH:60]=[CH:59][C:58]([C:61]#[N:62])=[C:57]([Cl:63])[C:56]=1[CH3:64])[C:40]([NH:42][NH:43][C:44](=O)[C:45]1[CH:50]=[CH:49][C:48]([C:51]#[N:52])=[CH:47][CH:46]=1)=[O:41])([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30]>C(Cl)Cl>[Si:29]([O:36][CH2:37][CH2:38][C@@H:39]([NH:54][C:55]1[CH:60]=[CH:59][C:58]([C:61]#[N:62])=[C:57]([Cl:63])[C:56]=1[CH3:64])[C:40]1[O:41][C:44]([C:45]2[CH:50]=[CH:49][C:48]([C:51]#[N:52])=[CH:47][CH:46]=2)=[N:43][N:42]=1)([C:32]([CH3:34])([CH3:33])[CH3:35])([CH3:31])[CH3:30]

Participants

6

Reactant 4

HCID 807IodineHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 59193077HCID 59193077, compound

Product 1

HCID 67006515HCID 67006515, compoundYield 98%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a 25 mL round bottom flask equipped with a magnetic stir bar and septum was added triphenylphosphine (polymer bound, 3.0 mmol/g loading) (1 g, 3 mmol) under an atmosphere of nitrogen. To this was added methylene chloride (60 mL) followed by addition of solid iodine (688 mg, 2.71 mmol). This was allowed to stir at room temperature for a period of 10 min followed by slow addition of triethylamine (1 mL, 7.24 mmol). (R)—N′-(4-(tert-butyldimethylsilyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)butanoyl)-4-cyanobenzohydrazide (950 mg, 1.81 mmol) was taken up in methylene chloride (15 mL) and slowly added to the stirred reaction mixture. After a period of 30 min, the solid polymer was filtered out and washed with additional methylene chloride (50 mL). The organic filtrate was then washed with 10% sodium thiosulfate/water (2×25 mL), brine (1×30 mL) and dried (Na2SO4). The solution was then filtered and concentrated under reduced to reveal a brown solid (1.03 g). Purification by flash column chromatography [EtOAc-hexanes (1:2) as eluent] afforded the title compound as a white crystalline solid (900 mg, 98%). 1H NMR (400 MHz, Acetone-d6, δ in ppm) 8.19 (d, J=9 Hz, 2H), 8.00 (d, J=9 Hz, 2H), 7.53 (d, J=9 Hz, 1H), 6.98 (d, J=9 Hz, 1H), 6.05 (d, J=9 Hz, 1H), 5.4 (m, 1H), 4.00-3.95 (m, 1H), 3.94-3.89 (m, 1H), 2.57-2.40 (m, 2H), 2.38 (s, 3H), 0.88 (s, 9H), 0.04 (s, 3H) and 0.00 (s, 3H).

Workup

  1. customTo a 25 mL round bottom flask equipped with a magnetic stir bar
  2. additionslowly added to the stirred reaction mixture
  3. waitAfter a period of 30 min
  4. filtrationthe solid polymer was filtered out
  5. washwashed with additional methylene chloride (50 mL)
  6. washThe organic filtrate was then washed with 10% sodium thiosulfate/water (2×25 mL), brine (1×30 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationThe solution was then filtered
  9. concentrationconcentrated
  10. customPurification by flash column chromatography [EtOAc-hexanes (1:2) as eluent]

Sources & evidence

ORD record
ord-c4f2dc3e9d4a455ab91677645fba87cd
Source dataset
uspto-grants-2011_11
Patent number
US08067448B2

Reaction notes

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