Tetrahydrofuran → Tert-butyl (5-bromo-3-(5-(3-methylthiophen-2-yl)-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)carbamate

HRID 78720

Reaction equation

HRID 78720 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([C:9]2[O:10][C:11]([C:14]3[S:15][CH:16]=[CH:17][C:18]=3[CH3:19])=[N:12][N:13]=2)[C:5]([NH2:8])=[N:6][CH:7]=1.C1COCC1.C(=O)(OC(C)(C)C)[O:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=O>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Br:1][C:2]1[N:3]=[C:4]([C:9]2[O:10][C:11]([C:14]3[S:15][CH:16]=[CH:17][C:18]=3[CH3:19])=[N:12][N:13]=2)[C:5]([NH:8][C:27](=[O:26])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 90495Di-tert-butyl dicarbonateHCID 594718295-Bromo-3-(5-(3-methylthiophen-2-yl)-1,3,4-oxadiazol-2-yl)pyrazin-2-amine

Product 1

HCID 86682777Tert-butyl (5-bromo-3-(5-(3-methylthiophen-2-yl)-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)carbamateYield 110.1%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

5-bromo-3-[5-(3-methyl-2-thienyl)-1,3,4-oxadiazol-2-yl]pyrazin-2-amine (11.49 g, 33.98 mmol) and DMAP (415.1 mg, 3.398 mmol) were suspended in DCM (172.4 mL) and THF (172.4 mL) and cooled in an icebath. tert-butoxycarbonyl tert-butyl carbonate (22.24 g, 101.9 mmol) was added portionwise. The reaction mixture was allowed to warm to ambient temperature and stirred for 2 hours. The reaction mixture was filtered through plug of silica gel and concentrated in vacuo. The residue was dissolved in ethylacetate, washed with aq NaHCO3 (×1), brine (×1), dried over MgSO4 and passed through short silica gel column. The mixture was concentrated in vacuo to low bulk, diluted with petrol and stirred at 50° C. for 5 min. The mixture was filtered to give tert-butyl (5-bromo-3-(5-(3-methylthiophen-2-yl)-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)carbamate as a colourless solid (16.4 g, 89%). H NMR (400.0 MHz, DMSO-d6) δ 1.4 (9H, s), 2.7 (3H, s), 7.0 (1H, d), 7.5 (1H, d), 8.7 (1H, s); LC/MS m/z 440.1 [M−100+1]+.

Workup

  1. filtrationThe reaction mixture was filtered through plug of silica gel
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was dissolved in ethylacetate
  4. washwashed with aq NaHCO3 (×1), brine (×1)
  5. dry with materialdried over MgSO4
  6. concentrationThe mixture was concentrated in vacuo to low bulk
  7. additiondiluted with petrol
  8. stirringstirred at 50° C. for 5 min
  9. filtrationThe mixture was filtered

Sources & evidence

ORD record
ord-a66d3b32df6d444daa45642181ca3499
Source dataset
uspto-grants-2014_09
Patent number
US08841449B2

Linked notes

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