Diisopropylethylamine → 4-(5-Cyano-[1,3,4]thiadiazol-2-ylamino)-piperidine-1-carboxylic acid tert-butyl ester

HRID 1426375Notes

Reaction equation

HRID 1426375 reaction equation
Cl[C:2]1[S:6][C:5]([C:7]#[N:8])=[N:4][N:3]=1.[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][CH:19]([NH2:22])[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].C(N(C(C)C)CC)(C)C>C(#N)C>[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][CH:19]([NH:22][C:2]2[S:6][C:5]([C:7]#[N:8])=[N:4][N:3]=2)[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:10])[CH3:11]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 12682914-Amino-1-Boc-piperidineHCID 112865425-Chloro-1,3,4-thiadiazole-2-carbonitrile

Product 1

HCID 593235714-(5-Cyano-[1,3,4]thiadiazol-2-ylamino)-piperidine-1-carboxylic acid tert-butyl esterYield 91.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 5-chloro-[1,3,4]thiadiazole-2-carbonitrile (0.5 g, 3.44 mmol) (prepared by a procedure similar to that described in U.S. Pat. No. 5,736,545), and 4-amino-piperidine-1-carboxylic acid tert-butyl ester (0.69 g, 3.44 mmol) and diisopropylethylamine (0.72 ml, 4.13 mmol) in acetonitrile (10 ml) was stirred at 130° C. for 30 min., under microwave irradiation. After this period, the solvent was evaporated in vacuo. The crude product was dissolved in dichloromethane and extracted with a saturated solution of ammonium chloride. The organic layer was separated, dried (Na2SO4) and the solvent evaporated in vacuo. The crude product was purified by short open column chromatography (silica gel; 3-5% ammonia in methanol (7M)/dichloromethane). The desired fractions were collected and evaporated in vacuo to yield D5 (0.97 g, 63%) as a white solid. C13H19N5O2S requires 309. Found 308 (MH+).

Workup

  1. customprepared by a procedure similar to
  2. waitAfter this period
  3. customthe solvent was evaporated in vacuo
  4. dissolutionThe crude product was dissolved in dichloromethane
  5. extractionextracted with a saturated solution of ammonium chloride
  6. customThe organic layer was separated
  7. dry with materialdried (Na2SO4)
  8. customthe solvent evaporated in vacuo
  9. customThe crude product was purified by short open column chromatography (silica gel; 3-5% ammonia in methanol (7M)/dichloromethane)
  10. customThe desired fractions were collected
  11. customevaporated in vacuo

Sources & evidence

ORD record
ord-43be422c1a0545a3ba6b67a9ec72c1ad
Source dataset
uspto-grants-2015_01
Patent number
US08933101B2

Reaction notes

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