Dimethyl Sulfide → HCID 68703599, compound

HRID 1518227Notes

Reaction equation

HRID 1518227 reaction equation
[CH:1]1([C:7]2[N:8]3[C:36]4[CH:35]=[C:34]([C:37]([O:39]C)=[O:38])[CH:33]=[CH:32][C:31]=4[CH2:30][CH:9]3[C:10]3[C:22](=O)[CH:21]([CH2:24][CH2:25][N:26]([CH3:28])[CH3:27])[CH2:20][C:19](=O)[C:11]=3[CH2:12][N:13]3[CH:18]=[CH:17][N:16]=[CH:15][C:14]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.S(C)C.[OH-].[Na+]>C1COCC1>[CH:1]1([C:7]2[N:8]3[C:36]4[CH:35]=[C:34]([C:37]([OH:39])=[O:38])[CH:33]=[CH:32][C:31]=4[CH2:30][CH:9]3[C:10]3[CH2:22][CH:21]([CH2:24][CH2:25][N:26]([CH3:28])[CH3:27])[CH2:20][CH2:19][C:11]=3[CH2:12][N:13]3[CH:18]=[CH:17][N:16]=[CH:15][C:14]=23)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

5

Reactant 3

HCID 1068Dimethyl SulfideHCID 14798Sodium HydroxideHCID 68702767HCID 68702767, compound

Product 1

HCID 68703599HCID 68703599, compoundYield 8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 11-cyclohexyl-2-[2-(dimethylamino)ethyl]-1,4-dioxo -1,2,3,4,17,17a-hexahydro-6H-indolo[2,1-a]pyrazino[2,1-d][2,5]benzodiazocine-14-carboxylate in THF (0.15 M), 20 eq of BH3.Me2S (2 M solution in THF) were added and the mixture was stirred overnight at RT. The solution was carefully quenched by adding 1.25 N HCl in MeOH until effervescence subsided. Then the volatiles were driven off by boiling the mixture to dryness. The crude residue was dissolved in MeOH (0.06 M) and 10 eq of 1N NaOH (aq) were added. The solution was stirred at 60° C. for 5 h. The solvent was evaporated in vacuo. The crude was then purified by prep RP-HPLC (stationary phase: column WATERS X-TERRA prep. C18, 5 microns. Mobile phase: MeCN/H2O buffered with 0.1% TFA). Fractions containing the pure compound were combined and freeze dried to afford the title compound as a white powder (8% yield from dimethyl 14-cyclohexyl-5,6,7,8-tetrahydroindolo[2,1-a][2,5]benzodiazocine-7,11-dicarboxylate). 1H NMR (400 MHz, DMSO-d6+TFA, 330 K) δ 8.15 (s, 1H), 7.93 (d, J 8.4, 1H), 7.90-7.85 (m, 1H), 7.76 (d, J 8.4, 1H), 7.70-7.60 (m, 2H), 7.59-7.49 (m, 1H), 4.50-4.40 (m, 1H), 4.30-4.20 (m, 1H), 4.00-3.80 (m, 2H), 3.80-3.70 (m, 1H), 3.70-3.50 (m, 2H), 3.40-3.20 (m, 5H), 2.79 (s, 6H), 2.80-2.70 (m, 2H), 2.70-2.60 (m, 2H), 2.00-1.80 (m, 3H), 1.80-1.60 (m, 2H), 1.60-1.50 (m, 1H), 1.40-1.10 (m, 4H); MS (ES+) m/z 501 (M+H)+.

Workup

  1. customThe solution was carefully quenched
  2. additionby adding 1.25 N HCl in MeOH until effervescence
  3. dissolutionThe crude residue was dissolved in MeOH (0.06 M)
  4. stirringThe solution was stirred at 60° C. for 5 h
  5. customThe solvent was evaporated in vacuo
  6. customThe crude was then purified by prep RP-HPLC (stationary phase: column WATERS X-TERRA prep. C18, 5 microns. Mobile phase: MeCN/H2O buffered with 0.1% TFA)
  7. additionFractions containing the pure compound
  8. customfreeze dried

Sources & evidence

ORD record
ord-38866e07fab84ea181a77f4cc8a7b078
Source dataset
uspto-grants-2012_07
Patent number
US08232390B2

Reaction notes

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