(Diethylamino)sulfur trifluoride → 7-N-(tert-Butoxycarbonyl)-8-[cyclopropyl(fluoro)methyl]-2-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-alpha]pyrazine

HRID 133069Notes

Reaction equation

HRID 133069 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]2[N:14]=[C:15]([C:17]([F:20])([F:19])[F:18])[N:16]=[C:10]2[CH:9]1[CH:21]([CH:23]1[CH2:25][CH2:24]1)O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(S(F)(F)[F:32])CC)C>ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]2[N:14]=[C:15]([C:17]([F:20])([F:19])[F:18])[N:16]=[C:10]2[CH:9]1[CH:21]([CH:23]1[CH2:25][CH2:24]1)[F:32])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 69364591[7-N-(tert-Butoxycarbonyl)-2-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-alpha]pyrazin-8-yl](cyclopropyl)methanol

Product 1

HCID 693627317-N-(tert-Butoxycarbonyl)-8-[cyclopropyl(fluoro)methyl]-2-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-alpha]pyrazine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 200 mg (0.55 mmol) of [7-N-(tert-butoxycarbonyl)-2-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-α]pyrazin-8-yl](cyclopropyl)methanol (prepared as outlined in Example 3, Step A) in 3.5 mL of dichloromethane was cooled to −78° C. and 0.406 mL (3.31 mmol) of (diethylamino)sulfur trifluoride (DAST) was added. The reaction mixture was stirred at −78° C. for 1 h, then warmed to ambient temperature and stirred overnight. The reaction mixture was partitioned between saturated aqueous sodium bicarbonate solution and dichloromethane. The aqueous phase was extracted with three portions of dichloromethane. The combined organic phases were washed with brine, dried over magnesium sulfate, and concentrated. Purification by HPLC (Gilson, YMC C-18, 10 to 90% acetonitrile/water gradient) gave the title compound.

Workup

  1. temperaturewarmed to ambient temperature
  2. stirringstirred overnight
  3. customThe reaction mixture was partitioned between saturated aqueous sodium bicarbonate solution and dichloromethane
  4. extractionThe aqueous phase was extracted with three portions of dichloromethane
  5. washThe combined organic phases were washed with brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated
  8. customPurification by HPLC (Gilson, YMC C-18, 10 to 90% acetonitrile/water gradient)

Sources & evidence

ORD record
ord-51ed2a7788284cdda7d42a8ccb64f9c4
Source dataset
uspto-grants-2008_06
Patent number
US07390809B2

Reaction notes

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