(Diethylamino)sulfur trifluoride → HCID 68456380, compound

HRID 751174Notes

Reaction equation

HRID 751174 reaction equation
[Cl:1][C:2]1[C:9]([CH3:10])=[C:8]([N:11]2[CH2:15][C@H:14]3[C@@H:16](O)[CH2:17][CH2:18][N:13]3[C:12]2=[O:20])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].CCN(S(F)(F)[F:27])CC>ClCCl>[Cl:1][C:2]1[C:9]([CH3:10])=[C:8]([N:11]2[CH2:15][CH:14]3[C@H:16]([F:27])[CH2:17][CH2:18][N:13]3[C:12]2=[O:20])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5]

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 59754344HCID 59754344, compound

Product 1

HCID 68456380HCID 68456380, compoundYield 47.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (7S,7aS)-2-chloro-4-(7-hydroxy-3-oxotetrahydropyrrolo[1,2-c]imidazol-2-yl)-3-methylbenzonitrile (WO 03/096980) (30 mg, 0.103 mmol) in dry dichloromethane (1.0 mL) was cooled to −65° C., treated with DAST (26 μL, 0.21 mmol) and stirred for 17 h, allowing the temperature to warm to rt. The reaction mixture was then cooled to 0° C., quenched with 10% sodium carbonate (0.5 mL) and extracted with CH2Cl2 (2×10 mL). The organic phase was washed with H2O (0.5 mL), dried (Na2SO4), filtered and concentrated under reduced pressure. The syrup was combined with a previous batch (5.4 mg) and chromatographed 3× (silica gel; EtOAc/hexane gradient then CH3OH/CH2Cl2 gradient) to yield the title compound (14.5 mg, 47.9%). HPLC: 99.1% at 2.04 min (retention time) (Conditions: YMC S-5 C-18 (4.6×50 mm), eluting with 0-100% B, 4 min gradient. (A=90% H2O—10% CH3C—0.1% TFA and B=10% H2O—90% CH3CN—0.1% TFA); Flow rate at 4 mL/min. UV detection at 220 nm). Chiral HPLC: retention time=20.8 min (100%); Conditions: OD (4.6×250 mm); Eluted with 20% isopropanol in heptane for 60 min at 1 mL/min. MS (ES+): m/z 294 [M+H]+.

Workup

  1. temperatureThe reaction mixture was then cooled to 0° C.
  2. customquenched with 10% sodium carbonate (0.5 mL)
  3. extractionextracted with CH2Cl2 (2×10 mL)
  4. washThe organic phase was washed with H2O (0.5 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customchromatographed 3× (silica gel

Sources & evidence

ORD record
ord-bdc6c462992e4457a8f77aebff926e18
Source dataset
uspto-grants-2008_07
Patent number
US07405234B2

Reaction notes

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