Sodium Carbonate → {3-[2-Chloro-5-(3,6-dihydro-2H-pyran-4-YL)-pyrimidin-4-yloxy]-cyclobutyl}-carbamic acid tert-butyl ester

HRID 1846825노트

반응식

HRID 1846825 반응식
[C:1]([O:5][C:6](=[O:21])[NH:7][CH:8]1[CH2:11][CH:10]([O:12][C:13]2[C:18](Br)=[CH:17][N:16]=[C:15]([Cl:20])[N:14]=2)[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[Na+].[Na+].CC1(C)C(C)(C)OB([C:36]2[CH2:37][CH2:38][O:39][CH2:40][CH:41]=2)O1>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:1]([O:5][C:6](=[O:21])[NH:7][CH:8]1[CH2:11][CH:10]([O:12][C:13]2[C:18]([C:36]3[CH2:41][CH2:40][O:39][CH2:38][CH:37]=3)=[CH:17][N:16]=[C:15]([Cl:20])[N:14]=2)[CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

참가 물질

7

반응물 3

HCID 10340Sodium CarbonateHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol esterHCID 58548640[3-(5-Bromo-2-chloro-pyrimidin-4-yloxy)-cyclobutyl]-carbamic acid tert-butyl ester

생성물 1

HCID 58548678{3-[2-Chloro-5-(3,6-dihydro-2H-pyran-4-YL)-pyrimidin-4-yloxy]-cyclobutyl}-carbamic acid tert-butyl ester수율 43.3%

시약·촉매·용매 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 312751,4-Dioxane용매

실험 절차

To a solution of [3-(5-bromo-2-chloro-pyrimidin-4-yloxy)-cyclobutyl]-carbamic acid tert-butyl ester (5.1 g, 13.3 mmol) in dioxane (80 mL) was treated with Na2CO3 (2.8 g, 26.6 mmol) in 15 mL of H2O as a solution, followed by additional of 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyran (3.3 g 16.0 mmol) and Pd(dppf)Cl2 (974 mg, 1.33 mmol). The resulting mixture was heated at refluxing overnight under N2 atmosphere. TLC showed that most of the staring materials were consumed completely. The solution was filtered, and the filter was concentrated. And the residue was purified by silica gel chromatography to give the product (2.2 g, 5.76 mmol, 43%). ESI-MS (M+1): 382 calc. for C18H24ClN3O4 381.

후처리

  1. temperatureThe resulting mixture was heated
  2. temperatureat refluxing overnight under N2 atmosphere
  3. customwere consumed completely
  4. filtrationThe solution was filtered
  5. concentrationthe filter was concentrated
  6. customAnd the residue was purified by silica gel chromatography

출처 및 근거

ORD 기록
ord-95ec245050c34860982a5e95d9e58115
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08952037B2

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