Dimethyl Sulfide → HCID 24872389, compound

HRID 1518235Notes

Reaction equation

HRID 1518235 reaction equation
[CH:1]1([C:7]2[C:15]3[CH:14]=[CH:13][C:12]([C:16]([O:18]C)=[O:17])=[CH:11][C:10]=3[N:9]3[CH2:20][C:21](=O)[C:22]4[C:23]5[C:28]([NH:29][CH:30]=4)=[CH:27][CH:26]=[CH:25][C:24]=5[C:8]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.S(C)C.[OH-].[Na+]>C1COCC1>[CH:1]1([C:7]2[C:15]3[CH:14]=[CH:13][C:12]([C:16]([OH:18])=[O:17])=[CH:11][C:10]=3[N:9]3[CH2:20][CH2:21][C:22]4[C:23]5[C:28]([NH:29][CH:30]=4)=[CH:27][CH:26]=[CH:25][C:24]=5[C:8]=23)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

5

Reactant 3

HCID 1068Dimethyl SulfideHCID 14798Sodium HydroxideHCID 68707112HCID 68707112, compound

Product 1

HCID 24872389HCID 24872389, compoundYield 12%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 13-cyclohexyl-6-oxo-6,7-dihydro-4H -indolo[4′,3′:3,4,5]azepino[1,2-a]indole-10-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 residue was dissolved in MeOH (0.06 M) and 10 eq of 1N NaOH (aq) were added. The solution stirred at 60° C. for 2 h before removing volatiles 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 (12% yield from methyl 3-cyclohexyl-1-[2-(dimethylamino)-2-oxoethyl]-1H,1′H-2,4′-biindole-6-carboxylate). 1H NMR (400 MHz, DMSO-d6+TFA, 300 K) δ 8.20 (s, 1H), 7.85 (d, J 8.4, 1H), 7.65 (d, J 8.4, 1H), 7.45 (d, J 7.9, 1H), 7.30-7.10 (m, 3H), 5.20-5.00 (m, 1H), 4.10-3.90 (m, 1H), 3.30-3.10 (m, 2H), 2.80-2.70 (m, 1H), 2.10-1.80 (m, 3H), 1.70-1.50 (m, 2H), 1.50-1.30 (m, 3H), 1.30-1.00 (m, 2H); MS (ES+) m/z 385 (M+H)+.

Workup

  1. customThe solution was carefully quenched
  2. additionby adding 1.25 N HCl in MeOH until effervescence
  3. dissolutionThe residue was dissolved in MeOH (0.06 M)
  4. stirringThe solution stirred at 60° C. for 2 h
  5. custombefore removing volatiles 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-2d5d77865acc474cac48009e260f2f8b
Source dataset
uspto-grants-2012_07
Patent number
US08232390B2

Reaction notes

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