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

HRID 1876903노트

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HRID 1876903 반응식
[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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 8857Ethyl Acetate용매

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온도
100 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-257a6c18da884357a34c4ffab36ab65e
출처 데이터셋
uspto-grants-2012_11
특허 번호
US08309718B2

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