Sodium Hydroxide → (7R)-7-[{2-[[4-(aminosulfonyl)butyl](methyl)amino]ethyl}(methyl)amino]-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylic acid

HRID 421948Notes

Reaction equation

HRID 421948 reaction equation
[OH-].[Na+].[NH2:3][S:4]([CH2:7][CH2:8][CH2:9][CH2:10][N:11]([CH3:45])[CH2:12][CH2:13][N:14]([CH3:44])[C@@H:15]1[CH2:22][N:21]2[C:23]3[CH:24]=[C:25]([C:36]([O:38]C)=[O:37])[CH:26]=[CH:27][C:28]=3[C:29]([CH:30]3[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]3)=[C:20]2[C:19]2[CH:40]=[CH:41][CH:42]=[CH:43][C:18]=2[O:17][CH2:16]1)(=[O:6])=[O:5]>CO>[NH2:3][S:4]([CH2:7][CH2:8][CH2:9][CH2:10][N:11]([CH3:45])[CH2:12][CH2:13][N:14]([CH3:44])[C@@H:15]1[CH2:22][N:21]2[C:23]3[CH:24]=[C:25]([C:36]([OH:38])=[O:37])[CH:26]=[CH:27][C:28]=3[C:29]([CH:30]3[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]3)=[C:20]2[C:19]2[CH:40]=[CH:41][CH:42]=[CH:43][C:18]=2[O:17][CH2:16]1)(=[O:5])=[O:6]

Participants

4

Reactant 2

HCID 14798Sodium Hydroxide2×HCID 66675081methyl (7R)-7-[{2-[[4-(aminosulfonyl)butyl](methyl)amino]ethyl}(methyl)amino]-1 4-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate

Product 1

HCID 66674696(7R)-7-[{2-[[4-(aminosulfonyl)butyl](methyl)amino]ethyl}(methyl)amino]-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylic acidYield 37%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

Sodium hydroxide (1N, 5 eq.) was added to a solution of methyl (7R)-7-[{2-[[4-(aminosulfonyl)butyl](methyl)amino]ethyl}(methyl)amino]-1 4-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate (0.03 M) in MeOH. The reaction was heated at 60° C. for 1 h prior to introducing further sodium hydroxide (2 N, 5 eq.) and continuing heating for 30 min. The reaction mixture was concentrated in vacuo, redissolved in DMSO and purified by RP-HPLC (WATERS XTERRA column, C18, 5um, 19×100 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 (37%) as a white powder. (ES+) m/z 597 (M+H)+.

Workup

  1. temperaturecontinuing heating for 30 min
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. dissolutionredissolved in DMSO
  4. custompurified by RP-HPLC (WATERS XTERRA column, C18, 5um, 19×100 mm. Mobile phase: MeCN/H2O buffered with 0.1% TFA)
  5. additionFractions containing the pure compound
  6. customfreeze dried

Sources & evidence

ORD record
ord-0ab98a796fbc4365bbb16adc115fae43
Source dataset
uspto-grants-2012_01
Patent number
US08101595B2

Reaction notes

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