Potassium Phosphate, Tribasic → 5-((4-chloro phenyl) (hydroxy)methyl)-6-(2-isopropylphenyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

HRID 60445노트

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HRID 60445 반응식
Br[C:2]1[CH:24]=[N:23][C:5]2[N:6]([CH3:22])[C:7](=[O:21])[N:8]([CH2:11][CH2:12][CH2:13][O:14][CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][O:16]3)[C:9](=[O:10])[C:4]=2[C:3]=1[CH:25]([C:27]1[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=1)[OH:26].[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH:42]([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=1B(O)O)([CH3:44])[CH3:43]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:33][C:30]1[CH:31]=[CH:32][C:27]([CH:25]([OH:26])[C:3]2[C:4]3[C:9](=[O:10])[N:8]([CH2:11][CH2:12][CH2:13][O:14][CH:15]4[CH2:20][CH2:19][CH2:18][CH2:17][O:16]4)[C:7](=[O:21])[N:6]([CH3:22])[C:5]=3[N:23]=[CH:24][C:2]=2[C:46]2[CH:47]=[CH:48][CH:49]=[CH:50][C:45]=2[CH:42]([CH3:44])[CH3:43])=[CH:28][CH:29]=1

참가 물질

6

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 27734772-Isopropylbenzeneboronic acidHCID 1188755116-bromo-5-((4-chlorophenyl)(hydroxy)methyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

생성물 1

HCID 1188755455-((4-chloro phenyl) (hydroxy)methyl)-6-(2-isopropylphenyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione수율 93%

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 312751,4-Dioxane용매

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온도
80 °C

실험 절차

To a mixture of 6-bromo-5-((4-chlorophenyl)(hydroxy)methyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (50 mg, 0.093 mmol), Pd(dppf)Cl2 (7 mg, 0.01 mmol) and aq. 2N K3PO4 (0.4 mL) in dioxane (2 mL) was added 2-isopropylphenylboronic acid (30 mg, 0.183 mmol). The reaction was heated at 80° C. for 18 h, cooled to RT and filtered. The filtrate was extracted with EA (2×20 mL). The combined organic layers were washed with water (20 mL) and brine (15 mL), dried over Na2SO4 and concentrated to a residue which was purified by Prep TLC eluted with PE/EA (1:1) to give 5-((4-chloro phenyl) (hydroxy)methyl)-6-(2-isopropylphenyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (50 mg, 93% yield) as a white solid.

후처리

  1. temperaturecooled to RT
  2. filtrationfiltered
  3. extractionThe filtrate was extracted with EA (2×20 mL)
  4. washThe combined organic layers were washed with water (20 mL) and brine (15 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated to a residue which
  7. customwas purified by Prep TLC
  8. washeluted with PE/EA (1:1)

출처 및 근거

ORD 기록
ord-73a578e6878b49449aa4fbc314f51d37
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09440972B2

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