Water → tert-butyl 4-{2-[4-(2-chloro-5-methoxypyrimidin-4-yl)-1H-pyrazol-1-yl]-3-cyanopropyl}piperidine-1-carboxylate

HRID 1876903ノート

反応式

HRID 1876903 の反応式
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([O:9][CH3:10])=[CH:4][N:3]=1.[C:11]([CH2:13][CH:14]([N:29]1[CH:33]=[C:32](B2OC(C)(C)C(C)(C)O2)[CH:31]=[N:30]1)[CH2:15][CH:16]1[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]1)#[N:12].O1CCOCC1.C(=O)([O-])[O-].[Na+].[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>[Cl:1][C:2]1[N:7]=[C:6]([C:32]2[CH:31]=[N:30][N:29]([CH:14]([CH2:13][C:11]#[N:12])[CH2:15][CH:16]3[CH2:17][CH2:18][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:26])[CH3:27])=[O:23])[CH2:20][CH2:21]3)[CH:33]=2)[C:5]([O:9][CH3:10])=[CH:4][N:3]=1

参加物

8

反応物 5

HCID 962WaterHCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 6014012,4-Dichloro-5-methoxypyrimidineHCID 68753948tert-butyl 4-(3-cyano-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propyl)piperidine-1-carboxylate

生成物 1

HCID 86637304tert-butyl 4-{2-[4-(2-chloro-5-methoxypyrimidin-4-yl)-1H-pyrazol-1-yl]-3-cyanopropyl}piperidine-1-carboxylate収率 76.7%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
100 °C

実験手順

To a mixture of 2,4-dichloro-5-methoxypyrimidine (0.967 g, 0.00540 mol), and tert-butyl 4-{3-cyano-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]propyl}piperidine-1-carboxylate (from example 1 step 3, 2.00 g, 0.00450 mol) in 1,4-dioxane (40 mL, 0.5 mol) was added a 1 M solution of sodium carbonate (0.954 g, 0.00900 mol) in water (8.99 mL, 0.499 mol) and tetrakis(triphenylphosphine)palladium(0) (0.4 g, 0.0003 mol). The reaction mixture was heated at 100° C. overnight. After cooling to room temperature, the mixture was diluted with EtOAc, washed with water, brine, dried over MgSO4, and concentrated. The residue was purified on silica gel, eluting with 0 to 80% EtOAc in hexanes, to provide the desired product (1.59 g, 76.64%). LCMS (M+Na) 483.4.

後処理

  1. temperatureAfter cooling to room temperature
  2. washwashed with water, brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customThe residue was purified on silica gel
  6. washeluting with 0 to 80% EtOAc in hexanes

出典と根拠

ORDレコード
ord-257a6c18da884357a34c4ffab36ab65e
出典データセット
uspto-grants-2012_11
特許番号
US08309718B2

反応ノート

読み込み中…