Potassium Phosphate, Tribasic → 6-(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)-2-(5-isopropyl-1H-indazol-4-yl)-4-methyl-5,6,7,8-tetrahydro-1,6-naphthyridine

HRID 80827노트

반응식

HRID 80827 반응식
Cl[C:2]1[CH:11]=[C:10]([CH3:12])[C:9]2[CH2:8][N:7]([C:13]3[N:17]([CH3:18])[N:16]=[C:15]([CH:19]4[CH2:21][CH2:20]4)[CH:14]=3)[CH2:6][CH2:5][C:4]=2[N:3]=1.[CH:22]([C:25]1[C:26](B2OC(C)(C)C(C)(C)O2)=[C:27]2[C:31](=[CH:32][CH:33]=1)[NH:30][N:29]=[CH:28]2)([CH3:24])[CH3:23].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.[Cl-].[Na+].O.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:19]1([C:15]2[CH:14]=[C:13]([N:7]3[CH2:6][CH2:5][C:4]4[N:3]=[C:2]([C:26]5[C:25]([CH:22]([CH3:24])[CH3:23])=[CH:33][CH:32]=[C:31]6[C:27]=5[CH:28]=[N:29][NH:30]6)[CH:11]=[C:10]([CH3:12])[C:9]=4[CH2:8]3)[N:17]([CH3:18])[N:16]=2)[CH2:21][CH2:20]1

참가 물질

9

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 712406515-isopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazoleHCID 866902762-chloro-6-(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)-4-methyl-5,6,7,8-tetrahydro-1,6-naphthyridine

생성물 1

HCID 712405116-(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)-2-(5-isopropyl-1H-indazol-4-yl)-4-methyl-5,6,7,8-tetrahydro-1,6-naphthyridine

시약·촉매·용매 5

HCID 178418397HCID 178418397, 화합물촉매2회HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매HCID 57417360Sodium chloride; water용매

실험 절차

Microwave was used to irradiated a solution of 2-chloro-6-(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)-4-methyl-5,6,7,8-tetrahydro-1,6-naphthyridine (30 mg, 0.099 mmol), crude 5-isopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole (38.2 mg, 0.119 mmol), Pd(PPh3)4 (11.45 mg, 9.91 μmol) and K3PO4 (42.1 mg, 0.198 mmol) in 1,4-dioxane (0.5 mL) and H2O (0.05 mL) at 130° C. for 1 h under nitrogen. Additional Pd(PPh3)4 (22.90 mg, 0.020 mmol) was added to the mixture. Microwave was irradiated to the mixture at 130° C. for further 2 h under nitrogen. The mixture was diluted with brine and EtOAc. The organic layer was separated, dried over Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography on 12 g of silica gel (eluent: DCM/MeOH=100:0 to 10:1) to give 6-(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)-2-(5-isopropyl-1H-indazol-4-yl)-4-methyl-5,6,7,8-tetrahydro-1,6-naphthyridine: 1H NMR (400 MHz, CDCl3) δ ppm 9.98 (br s, 1 H), 7.76 (d, J=0.76 Hz, 1H), 7.45-7.51 (m, 2 H), 7.12 (s, 1 H), 5.65 (s, 1 H), 4.11 (s, 2 H), 3.75 (s, 3 H), 3.30-3.33 (app t, 2 H), 3.15-3.24 (m, 3 H), 2.30 (s, 3 H), 1.87-1.94 (m, 1 H), 1.25 (d, J=7.07 Hz, 6 H), 0.89-0.94 (m, 2 H), 0.72-0.76 (m, 2 H); MS (ESI+) m/z 427.33 (M+H)+.

후처리

  1. customMicrowave was irradiated to the mixture at 130° C. for further 2 h under nitrogen
  2. customThe organic layer was separated
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash column chromatography on 12 g of silica gel (eluent: DCM/MeOH=100:0 to 10:1)

출처 및 근거

ORD 기록
ord-ccc514d6341a460db714794252b03abd
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846656B2

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