Triethylamine → 7-[(3-Chloro-4-fluoro-2-methylphenyl)carbonyl]-3-(1,2,4-thiadiazol-5-yl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine

HRID 1889110Notes

Reaction equation

HRID 1889110 reaction equation
[S:1]1[C:5]([C:6]2[N:10]3[CH2:11][CH2:12][NH:13][CH2:14][C:9]3=[N:8][N:7]=2)=[N:4][CH:3]=[N:2]1.C(N(CC)CC)C.[Cl:22][C:23]1[C:24]([CH3:33])=[C:25]([CH:29]=[CH:30][C:31]=1[F:32])[C:26](Cl)=[O:27].C([O-])(O)=O.[Na+]>C(Cl)Cl.CO.C(OCC)(=O)C>[Cl:22][C:23]1[C:24]([CH3:33])=[C:25]([C:26]([N:13]2[CH2:12][CH2:11][N:10]3[C:6]([C:5]4[S:1][N:2]=[CH:3][N:4]=4)=[N:7][N:8]=[C:9]3[CH2:14]2)=[O:27])[CH:29]=[CH:30][C:31]=1[F:32]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 665987953-(1,2,4-Thiadiazol-5-yl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazineHCID 866667393-Chloro-4-fluoro-2-methylbenzoyl chloride

Product 1

HCID 665994327-[(3-Chloro-4-fluoro-2-methylphenyl)carbonyl]-3-(1,2,4-thiadiazol-5-yl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine

Reagents, catalysts & solvents 3

HCID 887MethanolCatalystHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 3-(1,2,4-thiadiazol-5-yl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine (I115) (50 mg, 0.240 mmol) and triethylamine (0.050 mL, 0.360 mmol) in DCM (1.5 ml) was treated with 3-chloro-4-fluoro-2-methylbenzoyl chloride (I58) (54.7 mg, 0.264 mmol) in DCM (0.5 ml) and stirred at room temp for 1 h. After 1 h, 2 drops of methanol and then NaHCO3 solution (5 ml) and ethyl acetate (30 ml) were added. The product was extracted into the ethyl acetate which was dried (Na2SO4) and concentrated. Purification by high pH MDAP gave desired product as a white solid in 44 mg.

Workup

  1. waitAfter 1 h
  2. extractionThe product was extracted into the ethyl acetate which
  3. dry with materialwas dried (Na2SO4)
  4. concentrationconcentrated
  5. customPurification by high pH

Sources & evidence

ORD record
ord-ef6aa19073274985a3639a70e8c82e38
Source dataset
uspto-grants-2013_08
Patent number
US08501946B2

Reaction notes

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