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

HRID 579035노트

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HRID 579035 반응식
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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 4

HCID 178418807HCID 178418807, 화합물촉매2회HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

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온도
110 °C

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-511ba6b85af54edda10ec18169d2fc7c
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09040522B2

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