Hexane → Mavacamten

HRID 709420

반응식

HRID 709420 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.[CH3:13][C@H:14]([NH2:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.CCCCCC>O1CCOCC1>[CH:9]([N:5]1[C:4](=[O:12])[CH:3]=[C:2]([NH:21][C@H:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH3:13])[NH:7][C:6]1=[O:8])([CH3:11])[CH3:10]

참가 물질

5

반응물 3

HCID 8058HexaneHCID 758181-Phenethylamine, (-)-HCID 8201076-Chloro-3-(propan-2-yl)-1,2,3,4-tetrahydropyrimidine-2,4-dione

생성물 1

HCID 117761397Mavacamten수율 69%

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

반응 조건

온도
80 °C

실험 절차

To a solution of 6-chloro-3-isopropylpyrimidine-2,4(1H,3H)-dione (1.3, 1.0 g, 5.31 mmol) in 1,4-dioxane (20 mL) was added (S)-α-methylbenzylamine (Sigma-Aldrich, 1.43 g, 11.7 mmol, 2.2 equiv). The reaction mixture was stirred at 80° C. for 24 h. After cooling to ambient temperature, the mixture was concentrated under reduced pressure. The residual was taken up in EtOAc (70 mL) and washed with aqueous 1N HCl (2×50 mL) and brine (40 mL). The organic layer was dried with anhydrous Na2SO4 and then concentrated under reduced pressure to half the original volume to yield a precipitate. Hexane (20 mL) was added and the mixture was stirred at room temperature. The resulting solid was collected by filtration, washed with hexane (20 mL), and dried to yield 1.0 g (69%) of the title compound as a white solid. LC/MS: m/z (ES+) 274 (M+H)+.1H-NMR (400 MHz, d6-DMSO): δ 9.77 (s, 1H), 7.32 (m, 4H), 7.24 (m, 1H), 6.50 (d, J=6.8 Hz, 1H), 4.87 (m, 1H), 4.52 (m, 1H), 4.31 (d, J=6.8 Hz, 1H), 1.37 (m, 3H), 1.24 (m, 6H). 1H NMR (400 MHz, CD3OD) δ ppm 7.39-7.20 (m, 5H), 5.01 (m, 1H), 4.48 (m, 1H), 1.49 (d, J=6.7 Hz, 3H), 1.36 (m, 6H).

후처리

  1. temperatureAfter cooling to ambient temperature
  2. concentrationthe mixture was concentrated under reduced pressure
  3. washwashed with aqueous 1N HCl (2×50 mL) and brine (40 mL)
  4. dry with materialThe organic layer was dried with anhydrous Na2SO4
  5. concentrationconcentrated under reduced pressure to half the original volume
  6. customto yield a precipitate
  7. stirringthe mixture was stirred at room temperature
  8. filtrationThe resulting solid was collected by filtration
  9. washwashed with hexane (20 mL)
  10. customdried

출처 및 근거

ORD 기록
ord-b24d9eada67b43798c2f7abf0a0f041d
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09181200B2

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