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 80827ノート

反応式

HRID 80827 の反応式
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

参加物

9

反応物 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

生成物 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

試薬・触媒・溶媒 5

HCID 178418397HCID 178418397、化合物触媒2 回HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒HCID 57417360Sodium chloride; water溶媒

実験手順

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)+.

後処理

  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)

出典と根拠

ORDレコード
ord-ccc514d6341a460db714794252b03abd
出典データセット
uspto-grants-2014_09
特許番号
US08846656B2

反応ノート

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