N-methyl-2-pyrrolidone → (S)-6-((cyclopropyl(3-methoxyphenyl)methyl)amino)-3-isopropylpyrimidine-2,4(1H,3H)-dione

HRID 709422

반응식

HRID 709422 반응식
Cl[C:2]1[NH:7][C:6](=[O:8])[N:5]([CH:9]([CH3:11])[CH3:10])[C:4](=[O:12])[CH:3]=1.CN([C:16]1[C:21]2[C:22]([N:26](C)C)=[CH:23][CH:24]=[CH:25][C:20]=2[CH:19]=[CH:18][CH:17]=1)C.CN1[C:34](=[O:35])CCC1>>[CH:23]1([C@H:22]([NH:26][C:2]2[NH:7][C:6](=[O:8])[N:5]([CH:9]([CH3:11])[CH3:10])[C:4](=[O:12])[CH:3]=2)[C:21]2[CH:16]=[CH:17][CH:18]=[C:19]([O:35][CH3:34])[CH:20]=2)[CH2:24][CH2:25]1

참가 물질

4

반응물 3

HCID 13387N-methyl-2-pyrrolidoneHCID 88675Proton spongeHCID 8201076-Chloro-3-(propan-2-yl)-1,2,3,4-tetrahydropyrimidine-2,4-dione

생성물 1

HCID 117761892(S)-6-((cyclopropyl(3-methoxyphenyl)methyl)amino)-3-isopropylpyrimidine-2,4(1H,3H)-dione수율 11%

실험 절차

A solution of 6-chloro-3-isopropylpyrimidine-2,4(1H,3H)-dione (1.3, 50 mg, 0.265 mmol), (S)-cyclopropyl-(3-methoxyphenyl)methylamine (Sigma-Aldrich, 104 mg, 0.587 mmol), and proton sponge (85 mg, 0.397 mmol) in NMP (0.5 mL) was stirred at 130° C. for 2 h. After cooling to room temperature, the mixture was purified by preparative RP-HPLC (Shimadzu, Prominence LC-20AP system equipped with a Phenomenex Gemini-NX C18 column), eluting with 20-90% CH3CN in H2O (both containing 0.1% TFA). The fractions containing pure compound were combined and lyophilized to give 10 mg (11%) of the title compound as a white solid. LC/MS: m/z (ES+) 330 (M+H)+. 1H-NMR (400 MHz, CD3OD): δ ppm 7.26 (t, J=7.8 Hz, 6H), 6.92-6.79 (m, 3H), 5.00 (m, 1H), 3.79 (s, 3H), 3.74 (d, J=8.6 Hz, 1H), 1.36 (d, J=7.0 Hz, 6H), 1.23-1.13 (m, 1H), 0.68-0.60 (m, 1H), 0.58-0.50 (m, 1H), 0.50-0.42 (m, 1H), 0.41-0.34 (m, 1H).

후처리

  1. customthe mixture was purified by preparative RP-HPLC (Shimadzu, Prominence LC-20AP system
  2. customequipped with a Phenomenex Gemini-NX C18 column),
  3. washeluting with 20-90% CH3CN in H2O (both containing 0.1% TFA)
  4. additionThe fractions containing pure compound

출처 및 근거

ORD 기록
ord-468fc4bd33cd47518382530761c366e0
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09181200B2

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