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Sodium Carbonate → 2-(4-{2-(2,6-Dimethylphenyl)-5-[(5-isopropyl-2-methylphenoxy)methyl]-6-methylpyrimidin-4-yl}piperazin-1-yl)acetamide

HRID 1091944
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HRID 1091944 반응식
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][C:15]([NH2:17])=[O:16])[CH2:10][CH2:9]2)[C:5]([CH2:18][O:19][C:20]2[CH:25]=[C:24]([CH:26]([CH3:28])[CH3:27])[CH:23]=[CH:22][C:21]=2[CH3:29])=[C:4]([CH3:30])[N:3]=1.[CH3:31][C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([CH3:38])[C:33]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1>[CH3:31][C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([CH3:38])[C:33]=1[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][C:15]([NH2:17])=[O:16])[CH2:10][CH2:9]2)[C:5]([CH2:18][O:19][C:20]2[CH:25]=[C:24]([CH:26]([CH3:28])[CH3:27])[CH:23]=[CH:22][C:21]=2[CH3:29])=[C:4]([CH3:30])[N:3]=1
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5

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HCID 10340Sodium CarbonateHCID 5833222,6-Dimethylphenylboronic acidHCID 575315092-{4-[2-Chloro-5-(5-isopropyl-2-methyl-phenoxymethyl)-6-methyl-pyrimidin-4-yl]-piperazin-1-yl}-acetamide

생성물 1

HCID 575313962-(4-{2-(2,6-Dimethylphenyl)-5-[(5-isopropyl-2-methylphenoxy)methyl]-6-methylpyrimidin-4-yl}piperazin-1-yl)acetamide

시약·촉매·용매 1

HCID 31275
1,4-Dioxane
용매

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온도
100 °C

실험 절차

A mixture of 2-{4-[2-chloro-5-(5-isopropyl-2-methyl-phenoxymethyl)-6-methyl-pyrimidin-4-yl]-piperazin-1-yl}-acetamide (20 mg, 0.05 mmol), 2,6-dimethylphenylboronic acid (21 mg, 0.14 mmol) and 2 M sodium carbonate (0.14 mL, 0.28 mmol) in dioxane (1 mL) is degassed with bubbling argon for 20 min. Pd(PPh3)4 (2.9 mg, 5 mol %) is added and the reaction mixture is heated at 100° C. under nitrogen with magnetic stirring. After 18 h, the reaction mixture is partitioned between EtOAc (10 mL) and water (2 mL), the organic layer is separated, washed with brine (2 mL), dried over sodium sulfate, filtered and evaporated at reduced pressure to obtain a dark oil. Purification on silica gel (3% MeOH/CH2Cl2/0.1% NH4OH) provides the title compound as a colorless film. LC/MS (Method 3), M+H=502.3, Rt=2.43 min.; 1H NMR (CDCl3) δ=7.07-7.19 (m, 4H), 6.82 (m, 2H), 5.44 (br s, 1H), 4.97 (s, 2H), 3.57 (br s, 4H), 3.02 (s, 2H), 2.91 (m, 1H), 2.62 (m, 4H) 2.56 (s, 3H), 2.22 (s, 3H), 2.16 (s, 6H), 1.28 (d, 6H).

후처리

  1. customis degassed with bubbling argon for 20 min
  2. additionPd(PPh3)4 (2.9 mg, 5 mol %) is added
  3. customthe reaction mixture is partitioned between EtOAc (10 mL) and water (2 mL)
  4. customthe organic layer is separated
  5. washwashed with brine (2 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated at reduced pressure
  9. customto obtain a dark oil
  10. customPurification on silica gel (3% MeOH/CH2Cl2/0.1% NH4OH)

출처 및 근거

ORD 기록
ord-581118d947ae4db688feabe304603934
출처 데이터셋
uspto-grants-2012_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08129395B2

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