Sodium Bicarbonate → N-(tetrahydro-2H-pyran-4-ylmethyl)nicotinamide

HRID 579035ノート

反応式

HRID 579035 の反応式
BrC1C=NN([C:9]2[CH:24]=[CH:23][C:12]([C:13]([NH:15][CH2:16][CH:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[O:14])=[CH:11][N:10]=2)C=1OC.Cl.CN(C)C1C=C(B2OC(C)(C)C(C)(C)O2)C=CN=1.C(=O)(O)[O-].[Na+]>O1CCOCC1.O.CCOC(C)=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].C(Cl)Cl>[O:20]1[CH2:21][CH2:22][CH:17]([CH2:16][NH:15][C:13](=[O:14])[C:12]2[CH:23]=[CH:24][CH:9]=[N:10][CH:11]=2)[CH2:18][CH2:19]1

参加物

8

反応物 3

HCID 516892Sodium BicarbonateHCID 1176002516-(4-bromo-5-methoxy-1H-pyrazol-1-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)nicotinamideHCID 1212373412-(Dimethylamino)pyridine-4-boronic acid pinacol ester-HCl

生成物 1

HCID 69303415N-(tetrahydro-2H-pyran-4-ylmethyl)nicotinamide

試薬・触媒・溶媒 4

HCID 178418807HCID 178418807、化合物触媒2 回HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
110 °C

実験手順

Combined 6-(4-bromo-5-methoxy-1H-pyrazol-1-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)nicotinamide (80 mg, 0.202 mmol), N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine hydrochloride (173 mg, 0.607 mmol), PdCl2(dppf)-CH2Cl2 adduct (16.53 mg, 0.020 mmol) and sodium bicarbonate (136 mg, 1.619 mmol) in dioxane (0.6 mL) and water (0.15 mL) was let stir for 15 min. The mixture was then capped and heated at 110° C. for 1 h in the microwave. Additional PdCl2(dppf)-CH2Cl2 adduct (17 mg) was then added and the heating continued at 110° C. for 1 h in the microwave. The reaction mixture was diluted with EtOAc, concentrated onto Celite® and purified on a 10 g NH silica gel column eluted with 10 to 100% EtOAc in hexanes to give 64442-(dimethylamino)pyridin-4-yl)-5-methoxy-1H-pyrazol-1-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)nicotinamide as a brown oil. MS m/z 437 [M+H]+.

後処理

  1. customThe mixture was then capped
  2. concentrationconcentrated onto Celite®
  3. custompurified on a 10 g NH silica gel column
  4. washeluted with 10 to 100% EtOAc in hexanes

出典と根拠

ORDレコード
ord-511ba6b85af54edda10ec18169d2fc7c
出典データセット
uspto-grants-2015_05
特許番号
US09040522B2

反応ノート

読み込み中…