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Potassium Phosphate, Tribasic → HCID 178437593, 화합물

HRID 1482892
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HRID 1482892 반응식
Cl[C:2]1[CH:3]=[N:4][C:5]([C:8]([C@H:10]2[CH2:15][CH2:14][C@H:13]([C:16]([O:18][CH3:19])=[O:17])[CH2:12][CH2:11]2)=[CH2:9])=[N:6][CH:7]=1.[F:20][CH:21]([F:45])[C:22]1[CH:27]=[CH:26][N:25]=[C:24]([NH:28][C:29]2[CH:34]=[C:33](B3OC(C)(C)C(C)(C)O3)[CH:32]=[C:31]([CH3:44])[CH:30]=2)[N:23]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.[Cl-].[Na+].O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:45][CH:21]([F:20])[C:22]1[CH:27]=[CH:26][N:25]=[C:24]([NH:28][C:29]2[CH:34]=[C:33]([C:2]3[CH:3]=[N:4][C:5]([C:8]([C@H:10]4[CH2:15][CH2:14][C@H:13]([C:16]([O:18][CH3:19])=[O:17])[CH2:12][CH2:11]4)=[CH2:9])=[N:6][CH:7]=3)[CH:32]=[C:31]([CH3:44])[CH:30]=2)[N:23]=1
참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트

참가 물질

9

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 584561714-(difluoromethyl)-N-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amineHCID 178437632HCID 178437632, 화합물

생성물 1

HCID 178437593HCID 178437593, 화합물

시약·촉매·용매 4

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 312751,4-Dioxane용매HCID 57417360Sodium chloride; water용매

반응 조건

온도
110 °C

실험 절차

A mixture of methyl trans-4-[1-(5-chloropyrimidin-2-yl)ethenyl]cyclohexanecarboxylate (8 mg, 0.028 mmol), 4-(difluoromethyl)-N-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyrimidin-2-amine (10.3 mg, 0.028 mmol), tris(dibenzylideneacetone)-dipalladium(0) (1.3 mg, 1.42 μmol), XPhos (1.36 mg, 2.85 μmol) and potassium phosphate tribasic (18 mg, 0.085 mmol) in 1,4-dioxane (2 mL) and water (0.5 mL) was stirred at 110° C. under a nitrogen atmosphere for 3 hours. After cooling to room temperature, the mixture was diluted with brine and extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (ethyl acetate/petroleum ether) to afford methyl trans-4-{1-[5-(3-{[4-(difluoromethyl)pyrimidin-2-yl]amino}-5-methylphenyl)pyrimidin-2-yl]ethenyl}cyclohexanecarboxylate. MS ESI calc'd for C26H28F2N5O2 [M+H]+ 480. found 480. 1H NMR: (400 MHz, CDCl3) δ 8.94 (s, 2H), 8.72 (d, J=4.8 Hz, 1H), 8.62 (d, J=5.2 Hz, 1H), 7.88 (s, 1H), 7.37 (s, 1H), 7.13-7.11 (m, 1H), 7.04-7.03 (m, 1H), 6.43 (s, 1H), 5.48 (s, 1H), 3.69 (s, 3H), 3.09-3.06 (m, 1H), 2.46 (s, 3H), 2.05-2.02 (m, 3H), 1.69-1.62 (m, 3H), 1.39-1.33 (m, 3H).

후처리

  1. temperatureAfter cooling to room temperature
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by chromatography on silica gel (ethyl acetate/petroleum ether)

출처 및 근거

ORD 기록
ord-e411ffe44fb24c60a746be91048831f8
출처 데이터셋
uspto-grants-2016_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09416111B2

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