Tert-butyl 2,7-diazaspiro(3.5)nonane-7-carboxylate hydrochloride → tert-Butyl 2-(5-(2-(benzyloxy)-4-bromo-6-fluorophenyl)-1,3,4-thiadiazol-2-yl)-2,7-diazaspiro[3.5]nonane-7-carboxylate

HRID 579362Notes

Reaction equation

HRID 579362 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([Br:15])[CH:12]=[C:11]([F:16])[C:10]=1[C:17]1[S:18][C:19](Br)=[N:20][N:21]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH2:24]1[C:27]2([CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]2)[CH2:26][NH:25]1>O1CCOCC1.O>[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([Br:15])[CH:12]=[C:11]([F:16])[C:10]=1[C:17]1[S:18][C:19]([N:25]2[CH2:24][C:27]3([CH2:28][CH2:29][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:31][CH2:32]3)[CH2:26]2)=[N:20][N:21]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 45489808Tert-butyl 2,7-diazaspiro(3.5)nonane-7-carboxylate hydrochlorideHCID 867271872-(2-(Benzyloxy)-4-bromo-6-fluorophenyl)-5-bromo-1,3,4-thiadiazole

Product 1

HCID 86727186tert-Butyl 2-(5-(2-(benzyloxy)-4-bromo-6-fluorophenyl)-1,3,4-thiadiazol-2-yl)-2,7-diazaspiro[3.5]nonane-7-carboxylateYield 45%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a stirred suspension of 2-(2-(benzyloxy)-4-bromo-6-fluorophenyl)-5-bromo-1,3,4-thiadiazole (252 mg, 0.567 mmol) and tert-butyl 2,7-diazaspiro[3.5]nonane-7-carboxylate hydrochloride (179 mg, 0.681 mmol) in dioxane (2.8 mL) was added TEA (237 μL, 1.702 mmol) and the mixture was heated at 120° C. for 3 hours. The reaction mixture was cooled to RT, diluted with water (20 mL), extracted with DCM (20 mL). The organic phase was concentrated in vacuo to afford the crude product as a yellow oily residue. The crude material was purified by flash chromatography using a 40 g silica cartridge running an EtOAc/heptane gradient to afford the title compound as a white solid (150 mg, 45% yield). LC-MS: Rt 1.62 min; MS m/z 591.3 [M+H]+ [Method A]. 1H NMR (400 MHz, DMSO-d6) δ 7.29-7.47 (m, 7H), 5.31 (s, 2H), 3.83 (s, 4H), 3.17-3.30 (m, 4H), 1.65-1.77 (m, 4H), 1.40 (s, 9H).

Workup

  1. temperatureThe reaction mixture was cooled to RT
  2. extractionextracted with DCM (20 mL)
  3. concentrationThe organic phase was concentrated in vacuo
  4. customto afford the crude product as a yellow oily residue
  5. customThe crude material was purified by flash chromatography

Sources & evidence

ORD record
ord-a9a9c072407d4b6fa0349ca545050515
Source dataset
uspto-grants-2015_05
Patent number
US09040712B2

Reaction notes

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