Sodium Iodide → HCID 178424687, compound

HRID 1487825Notes

Reaction equation

HRID 1487825 reaction equation
C[O:2][CH2:3][C:4]1[NH:5][C:6]([C:10]2[C:11]([CH3:33])=[CH:12][C:13]([CH3:32])=[C:14]([CH:31]=2)[C:15]([N:17]2[CH2:22][CH2:21][CH:20]([C:23]3[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][CH:24]=3)[CH2:19][CH2:18]2)=[O:16])=[C:7]([CH3:9])[N:8]=1.[Na+].[I-].C1OCCOCCOCCOCCOC1.B(Br)(Br)Br>ClCCl>[OH:2][CH2:3][C:4]1[NH:5][C:6]([C:10]2[C:11]([CH3:33])=[CH:12][C:13]([CH3:32])=[C:14]([CH:31]=2)[C:15]([N:17]2[CH2:18][CH2:19][CH:20]([C:23]3[CH:24]=[CH:25][C:26]([C:27]#[N:28])=[CH:29][CH:30]=3)[CH2:21][CH2:22]2)=[O:16])=[C:7]([CH3:9])[N:8]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 25134Boron tribromideHCID 3633615-Crown-5HCID 178494665HCID 178494665, compound2×

Product 1

HCID 178424687HCID 178424687, compoundYield 17.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-30 °C

Procedure

Into a 50-mL 3-necked round-bottom flask, which was purged and maintained with an inert atmosphere of nitrogen, was placed a mixture of 4-(1-(5-(2-(methoxymethyl)-4-methyl-1H-imidazol-5-yl)-2,4-dimethylbenzoyl)piperidin-4-yl)benzonitrile (compound 2, 30 mg, 0.068 mmol), NaI (20 mg, 0.13 mmol), 15-crown-5 (30 mg, 0.14 mmol) and dichloromethane (10 mL). The mixture was cooled to −30° C. and boron tribromide (70 mg, 0.28 mmol) was added. The resulting mixture was allowed to warm to room temperature and stirred for 15 h. The reaction mixture was carefully quenched by the addition of saturated aqueous sodium bicarbonate (10 mL) and the resulting mixture was extracted dichloromethane (2×20 mL). The combined organics was washed with saturated aqueous Na2S2O3 (2×20 mL), then dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude product was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU)): Column, SunFire Prep C18 OBD Column, 5 um, 19*150 mm; mobile phase, water with 0.05% TFA and CH3CN (21% CH3CN up to 35% in 8 min, up to 100% in 2 min, down to 21% in 1 min); Detector, Waters 2489, 254&220 nm. The fractions containing pure compound were combined and lyophilized to yield the title compound as a white solid (5.0 mg, 17%). m/z (ES+) 429 (M+H)+. 1H NMR (400 MHz, CD3OD): δ 7.74-7.65 (m, 2), 7.48 (d, J=8.0 Hz, 2H), 7.38 (d, J=5.6 Hz, 1H), 7.29 & 7.16 (2 singlets, rotamers, Ar—H, 1H), ˜4.9 (1H obscured by water peak), 3.64 (app t, J=15.0 Hz, 1H), ˜3.35-3.21 (m, 1H partially overlapped with methanol solvent peak), 3.09-2.93 (m, 1H), 2.45 & 2.34 (2 singlets, rotamers, Ar—CH3, 3H), 2.29 (s, 3H), 2.24 (s, 3H), 2.09-1.97 (m, 1H), 1.92-1.71 (m, 2H), 1.70-1.55 (m, 1H).

Workup

  1. customInto a 50-mL 3-necked round-bottom flask, which was purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. temperatureto warm to room temperature
  4. customThe reaction mixture was carefully quenched by the addition of saturated aqueous sodium bicarbonate (10 mL)
  5. extractionthe resulting mixture was extracted dichloromethane (2×20 mL)
  6. washThe combined organics was washed with saturated aqueous Na2S2O3 (2×20 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude product was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU))
  11. waitmobile phase, water with 0.05% TFA and CH3CN (21% CH3CN up to 35% in 8 min
  12. waitup to 100% in 2 min
  13. waitdown to 21% in 1 min)
  14. additionThe fractions containing pure compound

Sources & evidence

ORD record
ord-5a7b4a5c43d048e9991ca4cc242bdc6e
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

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