Methanol → 4-{[(R)-[2-fluoro-3-(2-hy droxy ethoxy)-5-methoxyphenyl] (5-oxo-1-pyrimidi n-2-yl-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl]amino}benzamidine (R)-methoxyphenylacetate

HRID 2089687

반응식

HRID 2089687 반응식
Cl.[F:2][C:3]1[C:8]([O:9][CH2:10][CH2:11][OH:12])=[CH:7][C:6]([O:13][CH3:14])=[CH:5][C:4]=1[CH:15]([NH:28][C:29]1[CH:37]=[CH:36][C:32]([C:33]([NH2:35])=[NH:34])=[CH:31][CH:30]=1)[C:16]1[NH:20][C:19](=[O:21])[N:18]([C:22]2[N:27]=[CH:26][CH:25]=[CH:24][N:23]=2)[N:17]=1.CO.C(N(CC)CC)C.[CH3:47][O:48][C@H:49]([C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)[C:50]([OH:52])=[O:51]>C(O)(=O)C>[CH3:47][O:48][C@H:49]([C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)[C:50]([OH:52])=[O:51].[F:2][C:3]1[C:8]([O:9][CH2:10][CH2:11][OH:12])=[CH:7][C:6]([O:13][CH3:14])=[CH:5][C:4]=1[C@@H:15]([NH:28][C:29]1[CH:30]=[CH:31][C:32]([C:33]([NH2:35])=[NH:34])=[CH:36][CH:37]=1)[C:16]1[NH:20][C:19](=[O:21])[N:18]([C:22]2[N:23]=[CH:24][CH:25]=[CH:26][N:27]=2)[N:17]=1

참가 물질

6

반응물 4

HCID 887MethanolHCID 8471TriethylamineHCID 2724294(R)-(-)-alpha-methoxyphenylacetic acidHCID 1363340334-{[[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl](5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]-triazol-3-yl)methyl]amino}benzamidine hydrochloride

생성물 1

HCID 1363340344-{[(R)-[2-fluoro-3-(2-hy droxy ethoxy)-5-methoxyphenyl] (5-oxo-1-pyrimidi n-2-yl-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl]amino}benzamidine (R)-methoxyphenylacetate수율 38.8%

시약·촉매·용매 1

HCID 176Acetic Acid용매

반응 조건

온도
60 °C

실험 절차

A suspension of 4-{[[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl](5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]-triazol-3-yl)methyl]amino}benzamidine hydrochloride (4.73 g, purity 92%, 8.2 mmol) and methanol (131 mL) was heated to 60° C. to bring into solution. Triethylamine (1.71 mL, 12.3 mmol) was added thereto at 60° C., and the resulting mixture was stirred for minutes or more. To the suspension obtained, (R)-(−)-α-methoxyphenylacetic acid (2.73 g, 16.4 mmol) and acetic acid (4.35 mL) were added to bring the same into solution. The solution obtained was allowed to cool to 35° C., and a seed crystal of the captioned compound was added thereto, and the resulting mixture was stirred at room temperature for 20 hours and at 0° C. for 3 hours. The resulting solid was filtered, sequentially washed with ethanol (13 mL) and tert-butyl methyl ether (13 mL), and then dried at room temperature under reduced pressure to obtain the captioned compound (2.1 g) as a white solid.

후처리

  1. customTo the suspension obtained
  2. customThe solution obtained
  3. temperatureto cool to 35° C.
  4. additiona seed crystal of the captioned compound was added
  5. stirringthe resulting mixture was stirred at room temperature for 20 hours and at 0° C. for 3 hours
  6. filtrationThe resulting solid was filtered
  7. washsequentially washed with ethanol (13 mL) and tert-butyl methyl ether (13 mL)
  8. customdried at room temperature under reduced pressure

출처 및 근거

ORD 기록
ord-134261db91df471b9d896a7bd1157ef1
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08436009B2

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