Iodine → HCID 59193018, compound

HRID 470916Notes

Reaction equation

HRID 470916 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.II.[Si:22]([O:29][C@@H:30]([CH3:58])[C@@H:31]([NH:47][C:48]1[CH:53]=[CH:52][C:51]([C:54]#[N:55])=[C:50]([Cl:56])[C:49]=1[CH3:57])[C:32]([NH:34][NH:35][C:36]([C:38]1[CH:39]=[C:40]2[C:44](=[CH:45][CH:46]=1)[NH:43][CH:42]=[CH:41]2)=[O:37])=O)([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23]>C(Cl)Cl>[NH:43]1[C:44]2[C:40](=[CH:39][C:38]([C:36]3[O:37][C:32]([C@H:31]([NH:47][C:48]4[CH:53]=[CH:52][C:51]([C:54]#[N:55])=[C:50]([Cl:56])[C:49]=4[CH3:57])[C@@H:30]([O:29][Si:22]([C:25]([CH3:27])([CH3:26])[CH3:28])([CH3:23])[CH3:24])[CH3:58])=[N:34][N:35]=3)=[CH:46][CH:45]=2)[CH:41]=[CH:42]1

Participants

5

Reactant 3

HCID 807IodineHCID 11776TriphenylphosphineHCID 59193079HCID 59193079, compound

Product 1

HCID 59193018HCID 59193018, compoundYield 72.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Polymer supported Triphenylphosphine (640 mg, 1.58 mmol) was dissolved in 25 mL of DCM followed by addition of I2 (401 mg, 1.58 mmol) and TEA (0.59 mL, 4.24 mmol) at 0° C. N′-((2R,3S)-3-(tert-butyldimethylsilyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)butanoyl)-1H-indole-5-carbohydrazide (450 mg, 1.06 mmol) in 20 mL DCM was added to the pre-cooled solution mixture of PPh3/I2/TEA system and stirred. The reaction mixture was allowed to warm to room temperature and stirred for additional 10 minutes. The reaction was quenched with 20 mL saturated sodium thiosulfate and the biphasic mixture was separated. The aqueous layer was extracted with EtOAc (3×60 mL) and the combined organic extracts were dried (Na2SO4), filtered and concentrated under reduced pressure. The resulting crude oil was purified by flash chromatography [EtOAc-hexanes (1:1) as eluent] to provide the title compound (0.403 g, 72%). 1H NMR (500 MHz, Acetone d6, δ in ppm): 10.71 (br s, 1 H), 8.25 (br s, 1H), 7.78 (d, J=9 Hz, 1 H), 7.61 (d, J=9 Hz, 1 H), 7.49-7.47 (m, 1 H), 6.86 (d, J=9 Hz, 1 H), 6.64-6.62 (m, 1H) 5.55 (d, J=9 Hz, 1 H), 5.23 (d, 9 Hz, 1 H), 4.76-4.74 (m, 1 H), 2.44 (s, 3H), 1.48 (d, J=6 Hz, 3 H), 0.87 (s, 9 H), 0.12 (s, 3 H), −0.15 (s, 3 H).

Workup

  1. stirringstirred for additional 10 minutes
  2. customThe reaction was quenched with 20 mL saturated sodium thiosulfate
  3. customthe biphasic mixture was separated
  4. extractionThe aqueous layer was extracted with EtOAc (3×60 mL)
  5. dry with materialthe combined organic extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting crude oil was purified by flash chromatography [EtOAc-hexanes (1:1) as eluent]

Sources & evidence

ORD record
ord-10dcccbaab324cec86e1654ddc13509a
Source dataset
uspto-grants-2014_01
Patent number
US08629167B2

Reaction notes

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