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Diethyl Ether → tert-Butyl 4-(5-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate

HRID 1779004
ノート
印刷プレビュー

反応式

HRID 1779004 の反応式
CCOCC.Cl[C:7]1[N:12]=[C:11]([Cl:13])[C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][N:8]=1.[NH2:18][C:19]1[CH:20]=[CH:21][C:22]([CH:25]2[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][CH2:26]2)=[N:23][CH:24]=1.CCN(CC)CC>[Cl-].[Cl-].[Zn+2].ClCCCl.CC(O)(C)C>[Cl:13][C:11]1[C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][N:8]=[C:7]([NH:18][C:19]2[CH:20]=[CH:21][C:22]([CH:25]3[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][CH2:26]3)=[N:23][CH:24]=2)[N:12]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

8

反応物 4

HCID 3283Diethyl EtherHCID 8471TriethylamineHCID 27827742,4-Dichloro-5-(trifluoromethyl)pyrimidineHCID 59128562tert-Butyl 4-(5-aminopyridin-2-yl)piperidine-1-carboxylate

生成物 1

HCID 86712273tert-Butyl 4-(5-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate

試薬・触媒・溶媒 3

HCID 3007855
Zincchloride
触媒
HCID 111,2-Dichloroethane溶媒
HCID 6386tert-Butanol溶媒

実験手順

A 1.0 M ZnCl2 solution in Et2O (2.16 mL, 2.16 mmol) was added cautiously to a solution of 2,4-dichloro-5-(trifluoromethyl)pyrimidine (411 mg, 1.89 mmol) in 1:1 t-BuOH:DCE (100 mL) at room temperature and the resulting mixture stirred at room temperature for 20 minutes. tert-Butyl 4-(5-aminopyridin-2-yl)piperidine-1-carboxylate (K4) (500 mg, 1.80 mmol) was added followed by Et3N (0.30 mL, 2.16 mmol) then stirring was continued for 44 hours at room temperature. The volatiles were removed in vacuo and the residue was suspended in water (250 mL). The resulting suspension was sonicated for 10 minutes then filtered, washing the filter cake with water (2×100 mL). The filter cake was adsorbed onto silica gel and purified by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.) to give the title compound A44 as an off white solid (346 mg, 42%); 1H NMR (400 MHz, d6-DMSO) δ 10.74 (s, 1H), 8.81 (s, 1H), 8.73 (d, J=2.4 Hz, 1H), 8.00 (dd, J=8.5, 2.5 Hz, 1H), 7.30 (d, J=8.5 Hz, 1H), 4.05 (d, J=11.8 Hz, 2H), 2.82 (m, 3H), 1.81 (d, J=11.1 Hz, 2H), 1.55 (m, 2H), 1.41 (s, 9H). LCMS-A: rt 5.949 min; m/z 458 [M+H]+.

後処理

  1. customThe volatiles were removed in vacuo
  2. customThe resulting suspension was sonicated for 10 minutes
  3. filtrationthen filtered
  4. washwashing the filter cake with water (2×100 mL)
  5. custompurified by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.)

出典と根拠

ORDレコード
ord-f99558afdfc54f87b79d3e475dc36974
出典データセット
uspto-grants-2016_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09266864B2

反応ノート

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