Hexane → Mavacamten

HRID 709420

Reaction equation

HRID 709420 reaction equation
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]

Participants

5

Reactant 3

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

Product 1

HCID 117761397MavacamtenYield 69%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-b24d9eada67b43798c2f7abf0a0f041d
Source dataset
uspto-grants-2015_11
Patent number
US09181200B2

Linked notes

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