Sodium Iodide → (9aR)-benzyl 8-allyl-7-((R)-3-methyl-1-oxoisochroman-6-yl)hexahydro-1H-pyrazino[1,2-a]pyrazine-2(6H)-carboxylate

HRID 1501967Notes

Reaction equation

HRID 1501967 reaction equation
O[CH:2]([C:22]1[CH:23]=[C:24]2[C:29](=[CH:30][CH:31]=1)[C:28](=[O:32])[O:27][C@H:26]([CH3:33])[CH2:25]2)[CH2:3][N:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:11])[CH2:6][C@H:5]1[CH2:20]O.S(Cl)(Cl)=O.[CH2:38]([NH2:41])[CH:39]=[CH2:40].[I-].[Na+]>C(OCC)(=O)C>[CH2:38]([N:41]1[CH:2]([C:22]2[CH:23]=[C:24]3[C:29](=[CH:30][CH:31]=2)[C:28](=[O:32])[O:27][C@H:26]([CH3:33])[CH2:25]3)[CH2:3][N:4]2[CH2:9][CH2:8][N:7]([C:10]([O:12][CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[O:11])[CH2:6][C@H:5]2[CH2:20]1)[CH:39]=[CH2:40]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 7853AllylamineHCID 24386Thionyl ChlorideHCID 131734288(3S)-benzyl 4-(2-hydroxy-2-((R)-3-methyl-1-oxoisochroman-6-yl)ethyl)-3-(hydroxymethyl)piperazine-1-carboxylate

Product 1

HCID 131734289(9aR)-benzyl 8-allyl-7-((R)-3-methyl-1-oxoisochroman-6-yl)hexahydro-1H-pyrazino[1,2-a]pyrazine-2(6H)-carboxylate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A solution of (3S)-benzyl 4-(2-hydroxy-2-((R)-3-methyl-1-oxoisochroman-6-yl)ethyl)-3-(hydroxymethyl)piperazine-1-carboxylate (2.07 g, 4.55 mmol) in thionyl chloride (30.0 mL, 411 mmol) was heated at reflux for 1 h. After removing the volatiles, the residue was dissolved in N,N-dimethylformamide (20 mL) and treated with allylamine (1.879 mL, 25.05 mmol) at 0° C. The resulting solution was treated with sodium iodide (0.0680 g, 0.455 mmol) and heated at 90° C. for 1 h. The solution was diluted in ethyl acetate (300 mL) and was washed with saturated sodium bicarbonate three times, dried over sodium sulphate concentrated and the residue was purified on Biotage using 40-100% ethyl acetate/hexane to give the title compound: LC/MS: (M+1)+: 476.14.

Workup

  1. temperatureat reflux for 1 h
  2. customAfter removing the volatiles
  3. dissolutionthe residue was dissolved in N,N-dimethylformamide (20 mL)
  4. washwas washed with saturated sodium bicarbonate three times
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated
  7. customthe residue was purified on Biotage

Sources & evidence

ORD record
ord-8aeabae1b2994ff889e4271988d17ae4
Source dataset
uspto-grants-2015_12
Patent number
US09206199B2

Reaction notes

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