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

HRID 1846825ノート

反応式

HRID 1846825 の反応式
[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]

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-95ec245050c34860982a5e95d9e58115
出典データセット
uspto-grants-2015_02
特許番号
US08952037B2

反応ノート

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