Acetic Acid → 5-(2-chloro-3-methoxy-phenyl)-1-(2-fluoro-6-methyl-benzyl)-6-methyl-1H-pyrimidine-2,4-dione

HRID 1049117노트

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HRID 1049117 반응식
[F:1][C:2]1[CH:18]=[CH:17][CH:16]=[C:15]([C:19](F)(F)F)[C:3]=1[CH2:4][N:5]1[C:10]([CH3:11])=[C:9](I)[C:8](=[O:13])[NH:7][C:6]1=[O:14].[Cl:23][C:24]1[C:29]([O:30][CH3:31])=[CH:28][CH:27]=[CH:26][C:25]=1B1OC(C)(C)C(C)(C)O1.[OH-].[Na+].C(O)(=O)C>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]>[Cl:23][C:24]1[C:29]([O:30][CH3:31])=[CH:28][CH:27]=[CH:26][C:25]=1[C:9]1[C:8](=[O:13])[NH:7][C:6](=[O:14])[N:5]([CH2:4][C:3]2[C:15]([CH3:19])=[CH:16][CH:17]=[CH:18][C:2]=2[F:1])[C:10]=1[CH3:11]

참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 426062771-[2-fluoro-6-(trifluoromethyl)benzyl]-5-iodo-6-methylpyrimidine-2,4(1H,3H)-dioneHCID 450369072-(2-Chloro-3-methoxyphenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane

생성물 1

HCID 582393035-(2-chloro-3-methoxy-phenyl)-1-(2-fluoro-6-methyl-benzyl)-6-methyl-1H-pyrimidine-2,4-dione수율 70%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매

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온도
45 °C

실험 절차

Compound 1b (80 g, 0.19 mol), 7a (60.22 g, 0.22 mol), HP(t-Bu)3BF4 (13.01 g, 44.85 mmol), and Pd2(dba)3 (13.69 g, 14.95 mmol) were charged to the reaction vessel and purged with an inert atmosphere. Degassed THF (560 mL) was added followed by NaOH (31.45 g, 0.56 mol) in degassed water (128.8 mL) and the reaction warmed to 45° C. After 2 hours acetic acid (56 mL) was added and stirred for 15 minutes. After settling, the layers were separated and the organic layer was filtered through celite, rinsing with hot THF (2×160 mL). The filtrate was concentrated in vacuo to a slurry, to which was added N-acetyl cysteine (15.84 g) as a solution in water (160 mL) and ethanol (640 mL) and stirred for 2 hours at 75° C. under an inert atmosphere. The slurry was cooled to RT, and the solids filtered off, washed with ethanol:water (8:2, 2×160 mL) to give 5-(2-chloro-3-methoxy-phenyl)-1-(2-fluoro-6-methyl-benzyl)-6-methyl-1H-pyrimidine-2,4-dione 7b as a white solid (58.6 g, 0.13 mol, 70%).

후처리

  1. custompurged with an inert atmosphere
  2. additionDegassed THF (560 mL) was added
  3. customthe layers were separated
  4. filtrationthe organic layer was filtered through celite
  5. washrinsing with hot THF (2×160 mL)
  6. concentrationThe filtrate was concentrated in vacuo to a slurry, to which
  7. additionwas added N-acetyl cysteine (15.84 g) as a solution in water (160 mL)
  8. stirringethanol (640 mL) and stirred for 2 hours at 75° C. under an inert atmosphere
  9. temperatureThe slurry was cooled to RT
  10. filtrationthe solids filtered off
  11. washwashed with ethanol:water (8:2, 2×160 mL)

출처 및 근거

ORD 기록
ord-3846948a0ae34f768671892a91d1e07d
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09382214B2

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