Sodium Carbonate → N-(6-furo[3,2-b]pyridin-6-yl-1H-indazol-4-yl)-2-methyl-1,3-thiazole-4-carboxamide

HRID 520653ノート

反応式

HRID 520653 の反応式
[CH3:1][C:2]1[S:3][CH:4]=[C:5]([C:7]([NH:9][C:10]2[C:11]3[C:15]([CH:16]=[C:17](B4OC(C)(C)CC(C)(C)O4)[CH:18]=2)=[N:14][N:13](C2CCCCO2)[CH:12]=3)=[O:8])[N:6]=1.Br[C:36]1[CH:37]=[C:38]2[O:44][CH:43]=[CH:42][C:39]2=[N:40][CH:41]=1.O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+]>O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[O:44]1[C:38]2[C:39](=[N:40][CH:41]=[C:36]([C:17]3[CH:16]=[C:15]4[C:11]([CH:12]=[N:13][NH:14]4)=[C:10]([NH:9][C:7]([C:5]4[N:6]=[C:2]([CH3:1])[S:3][CH:4]=4)=[O:8])[CH:18]=3)[CH:37]=2)[CH:42]=[CH:43]1

参加物

7

反応物 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 226028096-Bromofuro[3,2-b]pyridineHCID 582558332-Methyl-N-[2-(tetrahydro-2H-pyran-2-yl)-6-(4,4,6,6-tetramethyl-1,3,2-dioxaborinan-2-yl)-2H-indazol-4-yl]-1,3-thiazole-4-carboxamide

生成物 1

HCID 53233429N-(6-furo[3,2-b]pyridin-6-yl-1H-indazol-4-yl)-2-methyl-1,3-thiazole-4-carboxamide

試薬・触媒・溶媒 2

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒

反応条件

温度
140 °C

実験手順

2-Methyl-N-[2-(tetrahydro-2H-pyran-2-yl)-6-(4,4,6,6-tetramethyl-1,3,2-dioxaborinan-2-yl)-2H-indazol-4-yl]-1,3-thiazole-4-carboxamide (50 mg), 6-bromofuro[3,2-b]pyridine (21 mg) and Pd(dppf)Cl2 (8 mg) were combined in a microwave vial. 1,4-Dioxane (0.5 ml) was added followed by sodium carbonate (44 mg) dissolved in water (0.5 ml). The reaction was heated in the microwave at 140° C. for 20 min. The reaction was filtered through a silica cartridge (1 g) washing with DCM:methanol (3:1). The solvent was then removed under a stream of nitrogen. The residue was dissolved in DMSO (1200 μl) and methanol (400 μl) and MDAP (method M). The product-containing fractions were left overnight, then concentrated and the residue dissolved in 1,4-dioxane:water (2 ml, 1:1, v/v) and freeze-dried. The residue was dissolved in DCM, a few drops of TFA were added and the reaction left overnight. The residue was further purified by MDAP (method K) then dried under nitrogen blowdown to give title compound, 13 mg.

後処理

  1. filtrationThe reaction was filtered through a silica cartridge (1 g)
  2. washwashing with DCM:methanol (3:1)
  3. customThe solvent was then removed under a stream of nitrogen
  4. dissolutionThe residue was dissolved in DMSO (1200 μl)
  5. concentrationconcentrated
  6. dissolutionthe residue dissolved in 1,4-dioxane
  7. dry with materialwater (2 ml, 1:1, v/v) and freeze-dried
  8. dissolutionThe residue was dissolved in DCM
  9. additiona few drops of TFA were added
  10. waitthe reaction left overnight
  11. customThe residue was further purified by MDAP (method K)
  12. customthen dried under nitrogen

出典と根拠

ORDレコード
ord-994739a0823943d784ec58b3c3a6eced
出典データセット
uspto-grants-2016_05
特許番号
US09326987B2

反応ノート

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