Sodium Carbonate → 4-{5-[2-(3,4-Dimethoxy-phenyl)-imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-3-trifluoromethyl-pyridin-2-yl}-piperazine-1-carboxylic acid tert-butyl ester

HRID 2409558Notes

Reaction equation

HRID 2409558 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[S:15][C:14]3=[N:16][CH:17]=[C:18](I)[N:13]3[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][N:30]([C:33]2[C:38]([C:39]([F:42])([F:41])[F:40])=[CH:37][C:36](B3OC(C)(C)C(C)(C)O3)=[CH:35][N:34]=2)[CH2:29][CH2:28]1)=[O:26])([CH3:23])([CH3:22])[CH3:21].C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1>[C:20]([O:24][C:25]([N:27]1[CH2:28][CH2:29][N:30]([C:33]2[C:38]([C:39]([F:42])([F:40])[F:41])=[CH:37][C:36]([C:18]3[N:13]4[C:14]([S:15][C:11]([C:5]5[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=5)=[N:12]4)=[N:16][CH:17]=3)=[CH:35][N:34]=2)[CH2:31][CH2:32]1)=[O:26])([CH3:23])([CH3:21])[CH3:22]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 667169462-(3,4-Dimethoxy-phenyl)-5-iodo-imidazo[2,1-b][1,3,4]thiadiazoleHCID 66717282Tert-butyl 4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluoromethyl)pyridin-2-yl)piperazine-1-carboxylate

Product 1

HCID 672838244-{5-[2-(3,4-Dimethoxy-phenyl)-imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-3-trifluoromethyl-pyridin-2-yl}-piperazine-1-carboxylic acid tert-butyl esterYield 56%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 2-(3,4-dimethoxy-phenyl)-5-iodo-imidazo[2,1-b][1,3,4]thiadiazole (0.2 g, 0.517 mmol, 1 eq), PdCl2(Ph3P)2 (73 mg, 0.103 mmol, 0.2 eq), 4-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3-trifluoromethyl-pyridin-2-yl]-piperazine-1-carboxylic acid tert-butyl ester (0.354 g, 0.775 mmol, 1.5 eq) and Na2CO3 (2M aqueous solution, 1 mL) in dioxane (4 mL) was heated at 110° C. for 2.5 h. The reaction was cooled down to rt and solvents were removed under reduced pressure. The residue was treated with water, sonicated and filtered. The solid was washed with water and purified by column chromatography (Biotage, cHex/EtOac 10 to 100%) to afford the desired product (170 mg, 56%): HPLC-MS: (5-100% B in 8 min, 0.8 mL/min, 50° C.): tR=7.36 min, [M+H]+ m/z 591.2; 1H NMR (300 MHz, CDCl3) δ 8.98 (d, J=2.0 Hz, 1H), 8.56 (d, J=2.2 Hz, 1H), 7.62 (s, 1H), 7.42 (m, 2H), 6.95 (m, 1H), 3.98 (s, 3H), 3.96 (s, 3H), 3.57 (m, 4H), 3.31 (m, 4H), 1.50 (s, 9H).

Workup

  1. temperatureThe reaction was cooled down to rt
  2. customsolvents were removed under reduced pressure
  3. additionThe residue was treated with water
  4. customsonicated
  5. filtrationfiltered
  6. washThe solid was washed with water
  7. custompurified by column chromatography (Biotage, cHex/EtOac 10 to 100%)

Sources & evidence

ORD record
ord-0bcc95770e474fe0b868d30386b978b9
Source dataset
uspto-grants-2014_08
Patent number
US08815918B2

Reaction notes

Loading…