Methyl iodide → HCID 10076103, compound

HRID 2267611Notes

Reaction equation

HRID 2267611 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([NH:12][C@H:13]([C:15]([NH:17][C@@H:18]2[C:24](=[O:25])[NH:23][C:22]3[CH:26]=[CH:27][CH:28]=[CH:29][C:21]=3[S:20][C@@H:19]2[C:30]2[CH:35]=[C:34]([F:36])[CH:33]=[C:32]([F:37])[CH:31]=2)=[O:16])[CH3:14])=[O:11])[CH:5]=[C:6]([F:8])[CH:7]=1.[H-].[Na+].[CH3:40]I>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([NH:12][C@H:13]([C:15]([NH:17][C@@H:18]2[C:24](=[O:25])[N:23]([CH3:40])[C:22]3[CH:26]=[CH:27][CH:28]=[CH:29][C:21]=3[S:20][C@@H:19]2[C:30]2[CH:31]=[C:32]([F:37])[CH:33]=[C:34]([F:36])[CH:35]=2)=[O:16])[CH3:14])=[O:11])[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 9984504HCID 9984504, compound

Product 1

HCID 10076103HCID 10076103, compoundYield 80.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of N2-[(3,5-difluorophenyl)acetyl]-N1-[(2R,3R)-2-(3,5-difluorophenyl)-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepin-3-yl]-L-alaninamide (16) (85 mg, 0.16 mmol) in DMF (1 ml) was added a 60% suspension of NaH (6.6 mg, 0.165 mmol). The reaction was stirred at RT for 5 min and methyl iodide (23 mg, 0.16 mmol) was added via syringe. The reaction was stirred at RT for 3 h and was quenched with dropwise addition of 1N HCl, diluted with water and extracted with ethyl acetate. The organic phase was collected and washed with H2O, dried, filtered and evaporated to yield a crude oil (85 mg). The crude product was purified by flash chromatography (50% ethyl acetate/hexanes) to afford the title compound (17) (70 mg, 80%) as a 1:1 mixture with the 2S,3S diastereomer as a white solid. 1H NMR (300 MHz, CDCl3) δ0.99 (d, 1.5H), 1.17 (d, 1.5H), 3.44 (s, 1H), 3.46 (s, 1H), 3.50 (s, 3H), 4.24 (m, 1H), 4.70 (m, 1H), 5.15 (m, 1H), 5.77 (d, 0.5H), 5.91 (d, 0.5H), 6.46 (dd, 1H), 6.65-6.92 (m, 6H), 7.31 (m, 2H), 7.51 (m, 1H), 7.71 (m, 1H). MS APCI, m/z=546 (M+1). LC/MS: 2.80 min.

Workup

  1. stirringThe reaction was stirred at RT for 3 h
  2. customwas quenched with dropwise addition of 1N HCl
  3. additiondiluted with water
  4. extractionextracted with ethyl acetate
  5. customThe organic phase was collected
  6. washwashed with H2O
  7. customdried
  8. filtrationfiltered
  9. customevaporated
  10. customto yield a crude oil (85 mg)
  11. customThe crude product was purified by flash chromatography (50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-e034e4f42e1f404888d2a22080df0b37
Source dataset
uspto-grants-2010_12
Patent number
US07858776B2

Reaction notes

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