1,2-Dichloroethane → (R)-N-(5-(4-(5-(2-(3-fluorophenyl)acetamido)-1,3,4-thiadiazol-2-yl)butyl)-1,3,4-thiadiazol-2-yl)-3,4-dihydroxybutanamide

HRID 538091Notes

Reaction equation

HRID 538091 reaction equation
[CH2:1]([C:11]1[S:15][C:14]([NH2:16])=[N:13][N:12]=1)[CH2:2][CH2:3][CH2:4][C:5]1[S:9][C:8]([NH2:10])=[N:7][N:6]=1.[F:17][C:18]1[CH:19]=[C:20]([CH2:24][C:25]([OH:27])=O)[CH:21]=[CH:22][CH:23]=1.CC1(C)[O:33][C@H:32]([CH2:34][C:35](O)=[O:36])[C:31](=O)[O:30]1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C.O.CCN(CC)CC>[F:17][C:18]1[CH:19]=[C:20]([CH2:24][C:25]([NH:10][C:8]2[S:9][C:5]([CH2:4][CH2:3][CH2:2][CH2:1][C:11]3[S:15][C:14]([NH:16][C:35](=[O:36])[CH2:34][C@@H:32]([OH:33])[CH2:31][OH:30])=[N:13][N:12]=3)=[N:6][N:7]=2)=[O:27])[CH:21]=[CH:22][CH:23]=1

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 676173-Fluorophenylacetic acidHCID 757711-HydroxybenzotriazoleHCID 108449602-((4R)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl)acetic acidHCID 574062125,5'-Butane-1,4-Diylbis(1,3,4-Thiadiazol-2-Amine)

Product 1

HCID 86687866(R)-N-(5-(4-(5-(2-(3-fluorophenyl)acetamido)-1,3,4-thiadiazol-2-yl)butyl)-1,3,4-thiadiazol-2-yl)-3,4-dihydroxybutanamideYield 12.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a suspension of diamine 1001 (400 mg, 1.56 mmol), 3-fluorophenylacetic acid (313 mg, 2.03 mmol), (R)-(−)-2,2-dimethyl-5-oxo-1,3-dioxolane-4-acetic acid (353 mg, 2.03 mmol) and Et3N (200 μL) in DMF (20 mL) at 0° C. was added HOBt (633 mg, 4.68 mmol) and followed by EDC (897 mg, 4.68 mmol). The mixture was stirred from 0° C. to room temperature over 18 h before it was diluted with water. The precipitate was collected by suction filtration and washed with water. The solid was further rinsed with a mixture of hot MeOH-THF. The combined filtrate was concentrated and purified by silica gel chromatography eluting with 1-10% MeOH in CH2Cl2 to provide (R)—N-(5-(4-(5-(2-(3-fluorophenyl)acetamido)-1,3,4-thiadiazol-2-yl)butyl)-1,3,4-thiadiazol-2-yl)-3,4-dihydroxybutanamide (1013, 93 mg).

Workup

  1. filtrationThe precipitate was collected by suction filtration
  2. washwashed with water
  3. washThe solid was further rinsed with a mixture of hot MeOH-THF
  4. concentrationThe combined filtrate was concentrated
  5. custompurified by silica gel chromatography
  6. washeluting with 1-10% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-11571c8796a4498d9e10c58d3d7ae7a2
Source dataset
uspto-grants-2014_10
Patent number
US08865718B2

Reaction notes

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