Diisopropylethylamine → tert-Butyl 2-(5-bromo-1,3,4-thiadiazol-2-yl)-2,7-diazaspiro[3.5]nonane-7-carboxylate

HRID 579355Notes

Reaction equation

HRID 579355 reaction equation
[Br:1][C:2]1[S:3][C:4](Br)=[N:5][N:6]=1.[CH2:8]1[C:11]2([CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)[CH2:10][NH:9]1.CCN(C(C)C)C(C)C>O1CCOCC1.O>[Br:1][C:2]1[S:3][C:4]([N:9]2[CH2:8][C:11]3([CH2:12][CH2:13][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:15][CH2:16]3)[CH2:10]2)=[N:5][N:6]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 30925302,5-Dibromo-1,3,4-thiadiazoleHCID 24820512tert-Butyl 2,7-diazaspiro[3.5]nonane-7-carboxylate

Product 1

HCID 86727178tert-Butyl 2-(5-bromo-1,3,4-thiadiazol-2-yl)-2,7-diazaspiro[3.5]nonane-7-carboxylateYield 88%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A stirred suspension of 2,5-dibromo-1,3,4-thiadiazole (245 mg, 1.004 mmol), tert-butyl 2,7-diazaspiro[3.5]nonane-7-carboxylate (290 mg, 1.105 mmol) and DIPEA (702 μL, 1.02 mmol) in dioxane (2.5 mL) was heated at 120° C. for 1 hour. The reaction mixture was diluted with water (10 mL), extracted with DCM (20 mL), and the organic phase was concentrated onto silica gel. The crude material was purified by flash chromatography using a 24 g silica cartridge running an EtOAc/heptane gradient to afford the title compound as a yellow oil (343 mg, 88% yield). LC-MS: Rt 1.25 min; MS m/z 391.2 [M+2]+ [Method A]. 1H NMR (400 MHz, Chloroform-d) δ 3.87 (s, 4H), 3.34-3.43 (m, 4H), 1.73-1.85 (m, 4H), 1.46 (s, 9H).

Workup

  1. extractionextracted with DCM (20 mL)
  2. concentrationthe organic phase was concentrated onto silica gel
  3. customThe crude material was purified by flash chromatography

Sources & evidence

ORD record
ord-f09887549fc84693a457f5acef494764
Source dataset
uspto-grants-2015_05
Patent number
US09040712B2

Reaction notes

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