Potassium Phosphate, Tribasic → 2-(4-Methyl-piperazin-1-yl)-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-4-ylamine

HRID 1191245ノート

反応式

HRID 1191245 の反応式
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)[C:5]([N+:15]([O-:17])=[O:16])=[C:4]([NH2:18])[CH:3]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[F:27][C:28]([F:39])([F:38])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1B(O)O>O1CCOCC1.O.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2].CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:14][N:11]1[CH2:12][CH2:13][N:8]([C:6]2[C:5]([N+:15]([O-:17])=[O:16])=[C:4]([NH2:18])[CH:3]=[C:2]([C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=3[C:28]([F:39])([F:38])[F:27])[N:7]=2)[CH2:9][CH2:10]1

参加物

8

反応物 3

HCID 62657Potassium Phosphate, TribasicHCID 27343872-(Trifluoromethyl)benzeneboronic acidHCID 866574286-Chloro-2-(4-methyl-piperazin-1-yl)-3-nitro-pyridin-4-ylamine

生成物 1

HCID 674108042-(4-Methyl-piperazin-1-yl)-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-4-ylamine

試薬・触媒・溶媒 4

HCID 167845palladium(II) acetate触媒HCID 12976736Bis(ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane);iron(2+)触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

A solution of 6-chloro-2-(4-methyl-piperazin-1-yl)-3-nitro-pyridin-4-ylamine (578 mg, 2.13 mmol, prepared as described in the previous step) in 1,4-dioxane (20 mL) was treated with K3PO4 (2.03 g, 9.58 mmol), 1,1′-bis(di-tert-butylphosphino)ferrocene (101 mg, 0.213 mmol), and 2-trifluoromethylphenylboronic acid (910 mg, 4.79 mmol). The resulting mixture was degassed via sonication, Pd(OAc)2 (47.8 mg, 0.213 mmol) was added, and the mixture was heated to 80° C. for 18 h. The cooled mixture was diluted with water (50 mL) and extracted twice with EtOAc (60 mL). The combined extracts were dried over MgSO4 and concentrated in vacuo. The residue was purified on a 40-g SEPRA Si 50 SPE column (Isco system: Flow rate=20 mL/min; Eluent=EtOAc-hexanes, 3:1 v/v for 5 min, then 3:1 to 1:0 v/v over 40 min) to yield 2-(4-methyl-piperazin-1-yl)-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-4-ylamine as an orange solid. 1H-NMR (400 MHz, CDCl3) δ: 7.74 (d, J=7.6 Hz, 1H), 7.55-7.61 (m, 1H), 7.45-7.54 (m, 2H), 6.13 (s, 1H), 6.02 (br. s., 2H), 3.46-3.52 (m, 4H), 2.44-2.50 (m, 4H), 2.32 (s, 3H). Mass Spectrum (LCMS, APCI pos.): Calculated for C17H18F3N5O2: 382.1 (M+H); Measured: 382.1.

後処理

  1. additionwas added
  2. extractionextracted twice with EtOAc (60 mL)
  3. dry with materialThe combined extracts were dried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified on a 40-g SEPRA Si 50 SPE column (Isco system

出典と根拠

ORDレコード
ord-6c81171c4b2f4be584f2b93041da385b
出典データセット
uspto-grants-2014_03
特許番号
US08680098B2

反応ノート

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