1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 14-cyclohexyl-6[2-(dimethylamino)ethyl]-N-(morpholin-4-ylsulfonyl)-5,6,7,8-tetrahydroindolo[2,1-a][2,5]benzodiazocine-11-carboxamide

HRID 1714077Notes

Reaction equation

HRID 1714077 reaction equation
[Cl-].[Cl-].[C:3]([C:6]1[CH:7]=[CH:8][C:9]2[C:10]([CH:30]3[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]3)=[C:11]3[C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=4[CH2:16][NH+:15]([CH2:23][CH2:24][NH+:25]([CH3:27])[CH3:26])[CH2:14][CH2:13][N:12]3[C:28]=2[CH:29]=1)(O)=[O:4].[N:36]1([S:42]([NH2:45])(=[O:44])=[O:43])[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1.CCN=C=NCCCN(C)C>CN(C1C=CN=CC=1)C>[CH:30]1([C:10]2[C:9]3[CH:8]=[CH:7][C:6]([C:3]([NH:45][S:42]([N:36]4[CH2:41][CH2:40][O:39][CH2:38][CH2:37]4)(=[O:44])=[O:43])=[O:4])=[CH:29][C:28]=3[N:12]3[CH2:13][CH2:14][N:15]([CH2:23][CH2:24][N:25]([CH3:26])[CH3:27])[CH2:16][C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=4[C:11]=23)[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1

Participants

5

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 2767394-MorpholinesulfonamideHCID 8660497211-Carboxy-14-cyclohexyl-6-[2-(dimethylammonio)ethyl]-5,6,7,8-tetrahydroindolo-[2,1-a][2,5]benzodiazocin-6-ium dichloride

Product 1

HCID 6850842414-cyclohexyl-6[2-(dimethylamino)ethyl]-N-(morpholin-4-ylsulfonyl)-5,6,7,8-tetrahydroindolo[2,1-a][2,5]benzodiazocine-11-carboxamideYield 31%

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Procedure

To 11-carboxy-14-cyclohexyl-6-[2-(dimethylammonio)ethyl]-5,6,7,8-tetrahydroindolo-[2,1-a][2,5]benzodiazocin-6-ium dichloride (1 eq) (prepared from the product described in Example 20, Step 5, by iterative freeze drying in the presence of aqueous HCl) in DCM (0.06 M) was added morpholine-4-sulfonamide (1.5 eq), EDCI (1.5 eq) and DMAP (1.5 eq). The solution was stirred at RT overnight. The solvent was evaporated in vacuo and the crude was purified by automated RP-MS-HPLC (stationary phase: column Waters SYMMETRY prep. C18, 7 μm, 19×300 mm. 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 (31%).

Workup

  1. dry with materialdrying in the presence of aqueous HCl) in DCM (0.06 M)
  2. customThe solvent was evaporated in vacuo
  3. customthe crude was purified by automated RP-MS-HPLC (stationary phase: column Waters SYMMETRY prep. C18, 7 μm, 19×300 mm. Mobile phase: MeCN/H2O buffered with 0.1 TFA)
  4. additionFractions containing the pure compound
  5. customfreeze dried

Sources & evidence

ORD record
ord-53260fd0e7004b4eae6e135876d9ef0e
Source dataset
uspto-grants-2010_09
Patent number
US07795247B2

Reaction notes

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