1,1'-Thiocarbonyldiimidazole → tert-Butyl 8-(cyclopropylmethylene)-2-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[1,5-alpha]pyrazine-7(8H)-carboxylate

HRID 133070Notes

Reaction equation

HRID 133070 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].C1N=CN(C(N2C=NC=C2)=S)C=1>CN(C)C1C=CN=CC=1.ClC(Cl)C>[CH:23]1([CH:21]=[C:9]2[N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][CH2:12][N:11]3[N:14]=[C:15]([C:17]([F:18])([F:19])[F:20])[N:16]=[C:10]23)[CH2:25][CH2:24]1

Participants

5

Reactant 2

HCID 802641,1'-ThiocarbonyldiimidazoleHCID 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 69362860tert-Butyl 8-(cyclopropylmethylene)-2-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[1,5-alpha]pyrazine-7(8H)-carboxylate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 63651,1-DichloroethaneSolvent

Procedure

A solution of 100 mg (0.28 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), 52.4 mg (0.294 mmol) of 1,1-thiocarbonyldiimidazole, and 3.4 mg (0.028 mmol) of 4-(dimethylamino)pyridine in 2.0 mL of dichloroethane was stirred at reflux temperature for 17 h. The reaction mixture was cooled to ambient temperature and concentrated in vacuo. The residue was partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate. The aqueous phase was extracted with three portions of ethyl acetate. The combined organics were washed with brine, dried over magnesium sulfate and concentrated. Purification by preparative TLC (silica gel) gave the title compound as a clear semi-solid.

Workup

  1. temperatureat reflux temperature for 17 h
  2. concentrationconcentrated in vacuo
  3. customThe residue was partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate
  4. extractionThe aqueous phase was extracted with three portions of ethyl acetate
  5. washThe combined organics were washed with brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated
  8. customPurification by preparative TLC (silica gel)

Sources & evidence

ORD record
ord-ffb46fd82e0a4023b0a402c3da64673f
Source dataset
uspto-grants-2008_06
Patent number
US07390809B2

Reaction notes

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