Diiodomethane → 2-(4-(4-fluorobenzyl)-3-oxo-2,4-diazabicyclo[3.1.0]hexan-2-yl)-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide

HRID 1882491Notes

Reaction equation

HRID 1882491 reaction equation
[F:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][N:7]2[CH:11]=[CH:10][N:9]([C:12]3[S:13][C:14]([C:18]([NH:20][CH2:21][C:22]4[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=4)=[O:19])=[C:15]([CH3:17])[N:16]=3)[C:8]2=[O:28])=[CH:4][CH:3]=1.[CH2:31]([Zn]CC)C.ICI.[Cl-].[NH4+]>O1CCCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[CH:11]3[CH:10]([CH2:31]3)[N:9]([C:12]3[S:13][C:14]([C:18]([NH:20][CH2:21][C:22]4[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=4)=[O:19])=[C:15]([CH3:17])[N:16]=3)[C:8]2=[O:28])=[CH:29][CH:30]=1

Participants

6

Reactant 4

HCID 6346DiiodomethaneHCID 25517Ammonium ChlorideHCID 594812772-(3-(4-fluorobenzyl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl)-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamideHCID 178418750HCID 178418750, compound

Product 1

HCID 441936912-(4-(4-fluorobenzyl)-3-oxo-2,4-diazabicyclo[3.1.0]hexan-2-yl)-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamideYield 7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a 25-mL two-neck round bottom flask under argon was charged with 2-(3-(4-fluorobenzyl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl)-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide (0.10 g, 0.24 mmol) and tetrahydrofuran (5 mL). Diethylzinc in hexanes (0.35 mL of 1 M solution, 0.35 mmol) was added slowly with a syringe. The solution was stirred and maintained at ambient temperature while diiodomethane (0.10 g, 0.35 mmol) was added slowly with a syringe. The reaction mixture was stirred at 60° C. for 8 hours and cooled in an ice-water bath, followed by the addition of saturated aqueous ammonium chloride (5 mL). The mixture was extracted with ethyl acetate (80 mL) and washed with saturated aqueous ammonium chloride (2×8 mL), water (3×8 mL), dried over sodium sulfate and filtered. The filtrate was concentrated and purified by preparative thin layer chromatography eluted with dichloromethane/methanol (20/1) to afford the title compound in 7% yield (7 mg). 1H NMR (300 MHz, CDCl3) δ 8.57 (br, 2H), 7.66-7.63 (m, 1H), 7.35-7.26 (m, 2H), 7.20-7.18 (m, 1H), 7.06-7.00 (m, 2H), 6.31-6.29 (m, 1H), 4.87 (br s, 2H), 4.74 (br s, 2H), 3.00 (br s, 2H), 2.39 (s, 3H), 0.92-0.81 (m, 2H); MS (ES+) m/z 437.9 (M+1).

Workup

  1. additionwas added slowly with a syringe
  2. stirringThe reaction mixture was stirred at 60° C. for 8 hours
  3. temperaturecooled in an ice-water bath
  4. extractionThe mixture was extracted with ethyl acetate (80 mL)
  5. washwashed with saturated aqueous ammonium chloride (2×8 mL), water (3×8 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated
  9. custompurified by preparative thin layer chromatography
  10. washeluted with dichloromethane/methanol (20/1)

Sources & evidence

ORD record
ord-86c495c39343424ebbc2abe9a59db818
Source dataset
uspto-grants-2012_11
Patent number
US08318949B2

Reaction notes

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