Sodium Carbonate → Tert-butyl 4-{2-(2,6-diethylphenyl)-5-[(5-isopropyl-2-methylphenoxy)methyl]-6-methylpyrimidin-4-yl}piperazine-1-carboxylate

HRID 1455758

반응식

HRID 1455758 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([CH2:20][O:21][C:22]3[CH:27]=[C:26]([CH:28]([CH3:30])[CH3:29])[CH:25]=[CH:24][C:23]=3[CH3:31])=[C:18]([CH3:32])[N:17]=[C:16](Cl)[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:34]([C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([CH2:42][CH3:43])[C:37]=1B(O)O)[CH3:35].C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1>[CH2:34]([C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([CH2:42][CH3:43])[C:37]=1[C:16]1[N:15]=[C:14]([N:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]2)[C:19]([CH2:20][O:21][C:22]2[CH:27]=[C:26]([CH:28]([CH3:30])[CH3:29])[CH:25]=[CH:24][C:23]=2[CH3:31])=[C:18]([CH3:32])[N:17]=1)[CH3:35]

참가 물질

5

반응물 3

HCID 10340Sodium CarbonateHCID 18437832(2,6-Diethylphenyl)boronic acidHCID 575313954-[2-Chloro-5-(5-isopropyl-2-methyl-phenoxymethyl)-6-methyl-pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 11548705Tert-butyl 4-{2-(2,6-diethylphenyl)-5-[(5-isopropyl-2-methylphenoxy)methyl]-6-methylpyrimidin-4-yl}piperazine-1-carboxylate

시약·촉매·용매 1

HCID 1140Toluene용매

반응 조건

온도
90 °C

실험 절차

A mixture of 4-[2-chloro-5-(5-isopropyl-2-methyl-phenoxymethyl)-6-methyl-pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (700 mg, 1.47 mmol), 2,6-diethylphenylboronic acid (394 mg, 2.21 mmol), 2 M aqueous sodium carbonate (2.21 mL, 4.42 mmol) and toluene (5 mL) is degassed with argon bubbling for 15 min. Pd(PPh3)4 (87 mg, 5 mol %) is added and the resulting yellow-colored mixture is heated at 90° C. under nitrogen with magnetic stirring for 40 h. The reaction mixture is partitioned between EtOAc (50 mL) and water (15 mL), the organic layer is separated, washed with water (15 mL), bring (15 mL), dried over sodium sulfate, filtered and evaporated at reduced pressure to obtain a yellow liquid. Chromatography on a 30 g silica gel cartridge (10-30% EtOAc/Hexanes) affords the title compound as a colorless oil (along with recovered 4-[2-chloro-5-(5-isopropyl-2-methyl-phenoxymethyl)-6-methyl-pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester). LC/MS (Method 3), M+H=573.2, Rt=3.18 min.; 1H NMR (CDCl3) δ=7.26 (d, 1H), 7.12 (d, 3H), 6.83 (m, 2H), 4.99 (s, 2H), 3.51 (m, 4H), 2.90 (m, 6H), 2.55, (s, 3H), 2.42 (q, 4H) 2.24 (s, 3H), 1.28 (d, 6H), 1.10 (t, 6H).

후처리

  1. customis degassed with argon bubbling for 15 min
  2. additionPd(PPh3)4 (87 mg, 5 mol %) is added
  3. customThe reaction mixture is partitioned between EtOAc (50 mL) and water (15 mL)
  4. customthe organic layer is separated
  5. washwashed with water (15 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated at reduced pressure
  9. customto obtain a yellow liquid

출처 및 근거

ORD 기록
ord-7a56369ffc244725b4c0787e7971ce23
출처 데이터셋
uspto-grants-2009_01
특허 번호
US07482350B2

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