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 2409555ノート

反応式

HRID 2409555 の反応式
[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]

参加物

5

反応物 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

生成物 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 ester収率 102.5%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
110 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-807eee448183443fb639fb368a2b279f
出典データセット
uspto-grants-2014_08
特許番号
US08815918B2

反応ノート

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