Potassium Phosphate, Tribasic → tert-butyl 4-(2-(isoquinolin-5-yl)-5-(trifluoromethyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 2172313노트

반응식

HRID 2172313 반응식
B1([C:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH:11]=2)OC(C)(C)C(C)(C)O1.Br[C:24]1[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][C:25]=1I.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH:43]1[C:52]2[C:47](=[C:48](B(O)O)[CH:49]=[CH:50][CH:51]=2)[CH:46]=[CH:45][N:44]=1>O1CCOCC1.O.C(OCC)C>[CH:43]1[C:52]2[C:47](=[C:48]([C:24]3[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][C:25]=3[C:10]3[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:17])[CH2:12][CH:11]=3)[CH:49]=[CH:50][CH:51]=2)[CH:46]=[CH:45][N:44]=1

참가 물질

8

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 599474Isoquinoline-5-boronic acidHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 467352311-Bromo-2-iodo-4-(trifluoromethyl)benzene

생성물 1

HCID 89813602tert-butyl 4-(2-(isoquinolin-5-yl)-5-(trifluoromethyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate수율 76.2%

시약·촉매·용매 3

HCID 962Water용매HCID 3283Diethyl Ether용매HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

A solution of Cl2Pd(dppf)-CH2Cl2 adduct (Strem Chemicals Inc., Newburyport, Mass., 1.157 g, 1.416 mmol), (n-tert-butoxycarbonyl)-1,2,3,6-tetrahydropyridine-4-boronic acid pinacol ester (8.76 ml, 28.3 mmol), 1-bromo-2-iodo-4-(trifluoromethyl)benzene (9.94 g, 28.3 mmol), and potassium phosphate (36.1 g, 170 mmol) in 100 mL dioxane, 40 mL water was heated to 100° C. 3 hours. LC/MS showed complete consumption of starting material. Isoquinolin-5-ylboronic acid (4.90 g, 28.3 mmol) and Cl2Pd(AmPhos) (Sigma-Aldrich, St. Louis, Mo., 1.003 g, 1.416 mmol) were added, and the reaction mixture was again heated to 100° C. for an additional hour. The reaction mixture was allowed to cool to room temperature and was diluted with diethyl ether. The organics were washed with water, then brine, dried over MgSO4 and concentrated. Purification of the resulting residue by silica gel column chromatography (0 to 100% EtOAc/heptane) gave tert-butyl 4-(2-(isoquinolin-5-yl)-5-(trifluoromethyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate (9.80 g, 21.56 mmol).

후처리

  1. custom3 hours
  2. customconsumption of starting material
  3. temperatureto cool to room temperature
  4. washThe organics were washed with water
  5. dry with materialbrine, dried over MgSO4
  6. concentrationconcentrated
  7. customPurification of the resulting residue by silica gel column chromatography (0 to 100% EtOAc/heptane)

출처 및 근거

ORD 기록
ord-a726538d873e4aa999b7b4ecbb4dae92
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09051311B2

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