Diisopropylethylamine → HCID 178451167, compound

HRID 1035719Notes

Reaction equation

HRID 1035719 reaction equation
[C:1]([O:5][C:6]([C@@H:8]1[CH2:13][CH2:12][C@H:11]([O:14][C:15]2[CH:23]=[CH:22][C:18]([C:19]([OH:21])=O)=[CH:17][N:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.[Cl:33][C:34]1[CH:35]=[C:36]([CH:44]=[CH:45][CH:46]=1)[CH2:37][C:38]1[S:42][C:41]([NH2:43])=[N:40][N:39]=1>C(#N)C>[Cl:33][C:34]1[CH:35]=[C:36]([CH:44]=[CH:45][CH:46]=1)[CH2:37][C:38]1[S:42][C:41]([NH:43][C:19]([C:18]2[CH:22]=[CH:23][C:15]([O:14][C@@H:11]3[CH2:10][CH2:9][C@H:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:13][CH2:12]3)=[N:16][CH:17]=2)=[O:21])=[N:40][N:39]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 36685945-[(3-Chlorophenyl)methyl]-1,3,4-thiadiazol-2-amineHCID 178451168HCID 178451168, compound

Product 1

HCID 178451167HCID 178451167, compoundYield 49.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

0.321 g of cis-6-(4-tert-butoxycarbonylcyclohexyloxy)nicotinic acid (1 mmol, 1 eq.) is placed in 50 mL of acetonitrile at room temperature. 0.33 mL of diisopropylethylamine (2 mmol, 2 eq.), 0.466 g of bromotris-pyrrolidinophosphonium hexafluorophosphonate (1 mmol, 1 eq.) and 0.270 g of 5-(3-chlorobenzyl)[1.3.4]thiadiazol-2-ylamine (1.2 mmol, 1.2 eq.) are successively added with stirring. After 4 days at room temperature, the reaction medium is evaporated and 15 mL of DMF are added. The medium is stirred again for 18 hours, diluted in ethyl acetate, washed three times with brine, dried over magnesium sulfate, filtered and evaporated. The residue is chromatographed on silica gel, eluting with a gradient of ethyl acetate in heptane ranging from 5% to 50%. After evaporating the fractions of interest, the residue is chromatographed on silica gel with a gradient of ethyl acetate in dichloromethane ranging from 2% to 20%. 0.262 g of tert-butyl cis-4-{5-[5-(3-chlorobenzyl)[1.3.4]thiadiazol-2-ylcarbamoyl]pyridin-2-yloxy}cyclohexanecarboxylate is obtained.

Workup

  1. customthe reaction medium is evaporated
  2. addition15 mL of DMF are added
  3. stirringThe medium is stirred again for 18 hours
  4. additiondiluted in ethyl acetate
  5. washwashed three times with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue is chromatographed on silica gel
  10. washeluting with a gradient of ethyl acetate in heptane ranging from 5% to 50%
  11. customAfter evaporating the fractions of interest
  12. customthe residue is chromatographed on silica gel with a gradient of ethyl acetate in dichloromethane ranging from 2% to 20%

Sources & evidence

ORD record
ord-f2e09406e2524d4c91d9fcbf2edbae37
Source dataset
uspto-grants-2013_10
Patent number
US08546391B2

Reaction notes

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