Methanol → (5-(6-Chloro-4-(isopropylamino)pyridin-3-yl)-1,3,4-thiadiazol-2-yl)(3-(hydroxymethyl)pyrrolidin-1-yl)methanone

HRID 595394Notes

Reaction equation

HRID 595394 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([C:13]([O:15]C)=O)=[N:10][N:9]=2)=[C:4]([NH:17][CH:18]([CH3:20])[CH3:19])[CH:3]=1.[NH:21]1[CH2:27][CH2:26][CH2:25][C@H:22]1CO.[CH3:28][OH:29]>>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([C:13]([N:21]3[CH2:22][CH2:25][CH:26]([CH2:28][OH:29])[CH2:27]3)=[O:15])=[N:10][N:9]=2)=[C:4]([NH:17][CH:18]([CH3:20])[CH3:19])[CH:3]=1

Participants

4

Reactant 3

HCID 887MethanolHCID 640091L-ProlinolHCID 89690804Methyl 5-(6-chloro-4-(isopropylamino)pyridin-3-yl)-1,3,4-thiadiazole-2-carboxylate

Product 1

HCID 89691050(5-(6-Chloro-4-(isopropylamino)pyridin-3-yl)-1,3,4-thiadiazol-2-yl)(3-(hydroxymethyl)pyrrolidin-1-yl)methanone

Conditions

Temperature
80 °C

Procedure

To a stirred solution of methyl 5-(6-chloro-4-(isopropylamino)pyridin-3-yl)-1,3,4-thiadiazole-2-carboxylate (12) (60 mg, 0.1 mmol) in MeOH (2 mL), (S)-Prolinol (0.9 mmol, 5 equiv) was added and refluxed at 80° C. for 1 h. The reaction mixture was cooled and concentrated. The crude material obtained was purified by column chromatography through silica gel and MeOH: DCM as eluent to isolate the desired product, (5-(6-chloro-4-(isopropylamino)pyridin-3-yl)-1,3,4-thiadiazol-2-yl)(3-(hydroxymethyl)pyrrolidin-1-yl)methanone( ). LCMS: XBridge Phe 8, 4.6×30 mm, 3.5 μm; Solvent A=2% ACN: 98% H2O: 10 mM NH4COOH; Solvent B=98% ACN: 2% H2O: 10 mM NH4COOH; gradient 0-100% B over 1.5 min (3.2 min run time); retention time: 1.585 min; LCMS (ES-API), m/z 379.8 (M−H).

Workup

  1. temperatureThe reaction mixture was cooled
  2. concentrationconcentrated
  3. customThe crude material obtained
  4. customwas purified by column chromatography through silica gel and MeOH

Sources & evidence

ORD record
ord-796f50c8cb02407f897e95cb35f77d2d
Source dataset
uspto-grants-2016_01
Patent number
US09242975B2

Reaction notes

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