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

HRID 2409555Notes

Reaction equation

HRID 2409555 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]([N:27]1[CH2:32][CH2:31][N:30]([C:33]2[N:38]=[CH:37][C:36](B3OC(C)(C)C(C)(C)O3)=[CH:35][N:34]=2)[CH2:29][CH2:28]1)([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21].C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1>[C:23]([O:22][C:20]([N:27]1[CH2:32][CH2:31][N:30]([C:33]2[N:34]=[CH:35][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:37][N:38]=2)[CH2:29][CH2:28]1)=[O:21])([CH3:26])([CH3:24])[CH3:25]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 46739020tert-Butyl 4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-yl)piperazine-1-carboxylateHCID 667169462-(3,4-Dimethoxy-phenyl)-5-iodo-imidazo[2,1-b][1,3,4]thiadiazole

Product 1

HCID 667169444-{5-[2-(3,4-Dimethoxy-phenyl)-imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-pyrimidin-2-yl}-piperazine-1-carboxylic acid tert-butyl esterYield 102.5%

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 (0.3 g, 0.775 mmol, 1 eq), PdCl2(Ph3P)2 (0.11 g, 0.155 mmol, 0.2 eq), 2-(4-boc-piperazin-1-yl)pyrimidine-5-boronic acid pinacol ester (0.454 g, 1.16 mmol, 1.5 eq) and Na2CO3 (2M aqueous solution, 1.5 mL) in dioxane (4.5 mL) was heated at 110° C. for 2.5 h. The reaction was cooled down to it and solvents were removed under reduced pressure. The residue was treated with water, sonicated and filtered. The solid was washed with water, Et2O and dried to give the desired product (416 mg, 100%). HPLC-MS: (5-100% B in 8 min, 0.8 mL/min, 50° C.): tR=6.48 min, [M+H]+ m/z 524.2; 1H NMR (300 MHz, DMSO) δ 8.99 (s, 2H), 7.70 (s, 1H), 7.55 (d, J=8.4 Hz, 1H), 7.47 (s, 1H), 7.15 (d, J=8.4 Hz, 1H), 3.88 (s, 3H), 3.86 (s, 3H), 3.80 (m, 4H), 3.43 (m, 4H), 1.43 (s, 9H).

Workup

  1. temperatureThe reaction was cooled down to it and solvents
  2. customwere removed under reduced pressure
  3. additionThe residue was treated with water
  4. customsonicated
  5. filtrationfiltered
  6. washThe solid was washed with water, Et2O
  7. customdried

Sources & evidence

ORD record
ord-807eee448183443fb639fb368a2b279f
Source dataset
uspto-grants-2014_08
Patent number
US08815918B2

Reaction notes

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