Iodine → HCID 59841042, compound

HRID 1625155Notes

Reaction equation

HRID 1625155 reaction equation
[C:1]([O:5][C:6](=[O:31])[NH:7][CH:8]([C:10](=[O:30])[NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[C:13]=1[C:19](=O)[NH:20][C:21]1[CH:26]=[C:25]([F:27])[CH:24]=[C:23]([F:28])[CH:22]=1)[CH3:9])([CH3:4])([CH3:3])[CH3:2].C(N(CC)C(C)C)(C)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.II>C(Cl)Cl>[C:1]([O:5][C:6](=[O:31])[NH:7][CH:8]([C:10]1[O:30][C:19](=[N:20][C:21]2[CH:26]=[C:25]([F:27])[CH:24]=[C:23]([F:28])[CH:22]=2)[C:13]2[C:14]([Cl:18])=[CH:15][CH:16]=[CH:17][C:12]=2[N:11]=1)[CH3:9])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 807IodineHCID 11776TriphenylphosphineHCID 81531DiisopropylethylamineHCID 59841047HCID 59841047, compound

Product 1

HCID 59841042HCID 59841042, compoundYield 52%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
2.5 °C

Procedure

A 100-mL, three-neck, round bottomed flask equipped with a magnetic stirrer and thermometer was purged with nitrogen and charged with compound 168 (3.30 mmol), anhydrous methylene chloride (25 mL), N,N-diisopropylethylamine (4.60 g, 35.7 mmol) and triphenylphosphine (3.98 g, 15.2 mmol). The reaction mixture was then cooled to 0-5° C. in an ice/water bath. Iodine (3.61 g, 14.2 mmol) was then added portion-wise to the reaction mixture over 1 h. Once the addition was complete, the cooling bath was removed, and the mixture was stirred at room temperature for an additional 30 min. The reaction was then quenched with 10% aqueous potassium carbonate (25 mL), the organic layer separated, dried over sodium sulfate, filtered and concentrated under reduced pressure. Column chromatography of the resulting solid (silica gel, EtOAc/hexanes) gave a 52% yield of compound 169 as a white solid. m.p. 117-118° C.; 1H NMR (DMSO-d6) δ (ppm) 7.72-7.60 (m, 2H), 7.42 (dd, 1H, J=7.6 Hz, 1.3 Hz), 7.31 (d, 1H, J=7.0 Hz), 6.95 (t, 1H, J=9.3 Hz), 6.82 (m, 2H), 4.27 (m, 1H), 1.33 (s, 9H), 1.28 (d, 3H, J=7.2 Hz); m/z=436 (M+H). The reaction described above and compound 169 are shown below.

Workup

  1. customA 100-mL, three-neck, round bottomed flask equipped with a magnetic stirrer
  2. customthermometer was purged with nitrogen
  3. additionOnce the addition
  4. customthe cooling bath was removed
  5. customThe reaction was then quenched with 10% aqueous potassium carbonate (25 mL)
  6. customthe organic layer separated
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-013d9182e2674987b3cdd7c514cf2366
Source dataset
uspto-grants-2014_07
Patent number
US08779131B2

Reaction notes

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