Potassium Carbonate → 6-(2,4-Difluorophenoxy)-8-((r)-2-hydroxypropyl)-2-methylsulfanyl-8h-pyrido[2,3-d]pyrimidin-7-one

HRID 1393962노트

반응식

HRID 1393962 반응식
[OH:1][C@H:2]([CH3:15])[CH2:3][NH:4][C:5]1[C:10]([CH:11]=O)=[CH:9][N:8]=[C:7]([S:13][CH3:14])[N:6]=1.C[O:17][C:18](=O)[CH2:19][O:20][C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:22]=1[F:28].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[F:28][C:22]1[CH:23]=[C:24]([F:27])[CH:25]=[CH:26][C:21]=1[O:20][C:19]1[C:18](=[O:17])[N:4]([CH2:3][C@H:2]([OH:1])[CH3:15])[C:5]2[N:6]=[C:7]([S:13][CH3:14])[N:8]=[CH:9][C:10]=2[CH:11]=1

참가 물질

5

반응물 3

HCID 11430Potassium CarbonateHCID 23434554Methyl 2-(2,4-difluorophenoxy)acetateHCID 596814314-((r)-2-Hydroxy-propylamino)-2-methylsulfanyl-pyrimidine-5-carbaldehyde

생성물 1

HCID 596814396-(2,4-Difluorophenoxy)-8-((r)-2-hydroxypropyl)-2-methylsulfanyl-8h-pyrido[2,3-d]pyrimidin-7-one수율 59.1%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
60 °C

실험 절차

To a mixture of 4-((R)-2-hydroxy-propylamino)-2-methylsulfanyl-pyrimidine-5-carbaldehyde (17.7 g, 78 mmol) and (2,4-difluorophenoxy)acetic acid methyl ester (31.6 g, 156 mmol) in anhydrous dimethyl formamide (300 mL) was added potassium carbonate (30 g, 218 mmol). The reaction mixture was heated to 60° C. and after 18 hours, reaction mixture was cooled and DMF was distilled off. Residue suspended in water (300 mL) and extracted with dichloromethane, washed with brine and dried over magnesium sulfate. Filtered and concentrated under vacuum to give 29.5 g crude material which was chromatographed on silica gel column eluding with 1% methanol in dichloromethane to give 17.5 g 6-(2,4-difluorophenoxy)-8-((R)-2-hydroxypropyl)-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one (mass spec M+1=274).

후처리

  1. customreaction mixture
  2. temperaturewas cooled
  3. distillationDMF was distilled off
  4. extractionextracted with dichloromethane
  5. washwashed with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationFiltered
  8. concentrationconcentrated under vacuum
  9. customto give 29.5 g crude material which
  10. customwas chromatographed on silica gel column eluding with 1% methanol in dichloromethane

출처 및 근거

ORD 기록
ord-f07c55c5c78741c39132bf01968516de
출처 데이터셋
uspto-grants-2008_03
특허 번호
US07348331B2

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