Hexane → Mavacamten

HRID 709420

反応式

HRID 709420 の反応式
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]

参加物

5

反応物 3

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

生成物 1

HCID 117761397Mavacamten収率 69%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-b24d9eada67b43798c2f7abf0a0f041d
出典データセット
uspto-grants-2015_11
特許番号
US09181200B2

関連ノート

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