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Potassium Carbonate → tert-Butyl 4-(2-(1-(5-cyclopropylpyrimidin-2-yl)piperidin-4-yl)-2-methyl-2,3-dihydrobenzofuran-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 1025512
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HRID 1025512 반응식
Br[C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([CH:11]3[CH2:16][CH2:15][N:14]([C:17]4[N:22]=[CH:21][C:20]([CH:23]5[CH2:25][CH2:24]5)=[CH:19][N:18]=4)[CH2:13][CH2:12]3)([CH3:10])[CH2:7][C:6]=2[CH:26]=1.CC1(C)C(C)(C)OB([C:35]2[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][CH:36]=2)O1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:23]1([C:20]2[CH:19]=[N:18][C:17]([N:14]3[CH2:15][CH2:16][CH:11]([C:8]4([CH3:10])[CH2:7][C:6]5[CH:26]=[C:2]([C:35]6[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][CH:36]=6)[CH:3]=[CH:4][C:5]=5[O:9]4)[CH2:12][CH2:13]3)=[N:22][CH:21]=2)[CH2:25][CH2:24]1
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참가 물질

7

반응물 3

HCID 11430Potassium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 674689412-(4-(5-Bromo-2-methyl-2,3-dihydrobenzofuran-2-yl)piperidin-1-yl)-5-cyclopropylpyrimidine

생성물 1

HCID 68211506tert-Butyl 4-(2-(1-(5-cyclopropylpyrimidin-2-yl)piperidin-4-yl)-2-methyl-2,3-dihydrobenzofuran-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate수율 68.3%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매2회HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

To a degassed solution of 2-(4-(5-bromo-2-methyl-2,3-dihydrobenzofuran-2-yl)piperidin-1-yl)-5-cyclopropylpyrimidine (424 mg, 1.02 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (380 mg, 1.23 mmol), and K2CO3 (424 mg, 3.07 mmol) in dioxane (6 mL) and water (2 mL) was added Pd(Ph3P)4 (59.1 mg, 0.051 mmol). Upon completion of addition, the reaction mixture was heated in 100° C. oil bath for 3 hours. After this time, the reaction mixture was cooled to room temperature, diluted with water, and extracted with CH2Cl2 (3×5 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated to yield a residue. The residue was purified by column chromatography (silica gel, hexanes/EtOAc gradient 0 to 50% EtOAc) to afford Compound 11F as a white solid (360 mg, 0.697 mmol, 68% yield). 1H NMR (500 MHz, CDCl3) δ ppm 8.11 (s, 2 H), 7.15 (s, 1 H), 7.13 (d, J=8.5 Hz, 1 H), 6.65-6.71 (m, 1 H), 5.88 (br. s., 1 H), 4.75-4.87 (m, 2 H), 4.05 (br. s., 2 H), 3.73 (t, J=6.2 Hz, 1 H), 3.62 (t, J=5.5 Hz, 2 H), 3.16 (d, J=15.7 Hz, 1 H), 2.74-2.87 (m, 2 H), 2.39-2.54 (m, 2 H), 1.86-1.96 (m, 2 H), 1.76-1.84 (m, 1 H), 1.67-1.74 (m, 1 H), 1.61 (m, 1 H), 1.49 (s, 9 H), 1.37-1.41 (m, 3 H), 1.23-1.36 (m, 1 H), 0.84-0.92 (m, 2 H), 0.54-0.60 (m, 2 H). LC/MS (m/z)=517 (M+H)+.

후처리

  1. additionUpon completion of addition
  2. temperatureAfter this time, the reaction mixture was cooled to room temperature
  3. extractionextracted with CH2Cl2 (3×5 mL)
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto yield a residue
  8. customThe residue was purified by column chromatography (silica gel, hexanes/EtOAc gradient 0 to 50% EtOAc)

출처 및 근거

ORD 기록
ord-3a1f12e0bbd94774963acd83fe6af1b3
출처 데이터셋
uspto-grants-2014_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08729084B2

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