Diisopropylethylamine → [5-(2-Chloro-6-methyl-pyridin-4-yl)-3-(2,2-difluoro-benzo[1,3]dioxol-5-ylamino)-[1,2,4]triazol-1-yl]acetic acid ethyl ester

HRID 1952183Notes

Reaction equation

HRID 1952183 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:23]=[C:24]([CH3:26])[N:25]=1)[C:5]([NH:7][CH:8]([NH:11][C:12]1[CH:22]=[CH:21][C:15]2[O:16][C:17]([F:20])([F:19])[O:18][C:14]=2[CH:13]=1)SC)=O.Cl.[CH2:28]([O:30][C:31](=[O:35])[CH2:32][NH:33][NH2:34])[CH3:29].C(N(C(C)C)C(C)C)C>CC(O)(C)C>[CH2:28]([O:30][C:31](=[O:35])[CH2:32][N:33]1[C:5]([C:4]2[CH:23]=[C:24]([CH3:26])[N:25]=[C:2]([Cl:1])[CH:3]=2)=[N:7][C:8]([NH:11][C:12]2[CH:22]=[CH:21][C:15]3[O:16][C:17]([F:20])([F:19])[O:18][C:14]=3[CH:13]=2)=[N:34]1)[CH3:29]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 11593468Acetic acid, 2-hydrazinyl-, ethyl ester, hydrochloride (1:1)HCID 866457122-Chloro-N-[(2,2-difluoro-benzo[1,3]dioxol-5-ylamino)-methylsulfanyl-methyl]-6-methyl-isonicotinamide

Product 1

HCID 59497767[5-(2-Chloro-6-methyl-pyridin-4-yl)-3-(2,2-difluoro-benzo[1,3]dioxol-5-ylamino)-[1,2,4]triazol-1-yl]acetic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Conditions

Temperature
60 °C

Procedure

Intermediate D2 (13.6 g; 0.0340 mol), 2-hydrazinylacetic acid ethyl ester, hydrochloride (1:1) (10.5 g; 0.0680 mol), N-ethyl-N-(1-methylethyl)-2-propanamine (13.2 g; 0.1020 mol) and t-BuOH (400 ml) were refluxed for 2 hours. The reaction mixture was then evaporated. Water was added and the product was extracted with CH2Cl2. The organic layer was dried on MgSO4, filtered and evaporated in vacuo. The residue was then heated to 60° C. in ethanol/HCl for 1 hour. The reaction mixture was partly evaporated and, the precipitate was filtered off and dried. Yield: 4.57 g of intermediate D3.

Workup

  1. customThe reaction mixture was then evaporated
  2. additionWater was added
  3. extractionthe product was extracted with CH2Cl2
  4. customThe organic layer was dried on MgSO4
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe reaction mixture was partly evaporated
  8. filtrationthe precipitate was filtered off
  9. customdried

Sources & evidence

ORD record
ord-19877f1f04394416b80a1aeff2f3b118
Source dataset
uspto-grants-2013_03
Patent number
US08404851B2

Reaction notes

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