Dichloromethane → HCID 69490986, compound

HRID 968643Notes

Reaction equation

HRID 968643 reaction equation
C(OC(N1CC(C)NC(C)C1)=O)(C)(C)C.[C:16]([O:20][C:21]([N:23]1[CH2:28][CH:27]([CH3:29])[N:26]([C:30]([C:32]2[C:40]3[C:35](=[C:36]([O:41][CH3:42])[CH:37]=[CH:38][CH:39]=3)[N:34]([CH2:43][CH:44]3[CH2:49][CH2:48][CH2:47][CH2:46][CH2:45]3)[CH:33]=2)=[O:31])[CH:25]([CH3:50])[CH2:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17].FC(F)(F)C(O)=O.[Cl:58]CCl>[OH-].[Na+]>[C:16]([O:20][C:21]([N:23]1[CH2:24][CH:25]([CH3:50])[N:26]([C:30]([C:32]2[C:40]3[C:35](=[C:36]([O:41][CH3:42])[CH:37]=[CH:38][CH:39]=3)[N:34]([CH2:43][CH:44]3[CH2:45][CH2:46][CH2:47][CH2:48][CH2:49]3)[CH:33]=2)=[O:31])[CH:27]([CH3:29])[CH2:28]1)=[O:22])([CH3:17])([CH3:18])[CH3:19].[ClH:58].[CH:44]1([CH2:43][N:34]2[C:35]3[C:40](=[CH:39][CH:38]=[CH:37][C:36]=3[O:41][CH3:42])[C:32]([C:30]([N:26]3[CH:25]([CH3:50])[CH2:24][NH:23][CH2:28][CH:27]3[CH3:29])=[O:31])=[CH:33]2)[CH2:49][CH2:48][CH2:47][CH2:46][CH2:45]1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 22219990Tert-butyl 3,5-dimethylpiperazine-1-carboxylateHCID 69490986HCID 69490986, compound

Product 2

HCID 69490986HCID 69490986, compoundHCID 131726701HCID 131726701, compound

Reagents, catalysts & solvents 1

HCID 14798Sodium HydroxideSolvent

Procedure

4-{[1-(Cyclohexylmethyl)-7-methoxy-1H-indol-3-yl]carbonyl}-3,5-dimethylpiperazine-1-carboxylic acid tert-butyl ester was prepared following the method in Example 10 using 3,5-dimethylpiperazine-1-carboxylic acid tert-butyl ester (E. J. Jacobsen et al; J. Med. Chem. 42, 1123-1144, 1999) instead of 2,3,5,6-tetramethylpiperazine. To an ice cooled solution of 4-{[1-(cyclohexylmethyl)-7-methoxy-1H-indol-3-yl]carbonyl}-3,5-dimethylpiperazine-1-carboxylic acid tert-butyl ester (0.52 g, 1.08 mmol) in dichloromethane (5 ml) was added dropwise trifluoroacetic acid (2 ml). The mixture was allowed to warm to room temperature over 2 h before removal of any volatile components under reduced pressure. The residue was then suspended in 5 M sodium hydroxide solution (10 ml) and extracted into dichloromethane (2×30 ml). The combined organic layers were dried with magnesium sulfate and evaporated to an oil. This was purified by flash chromatography eluting with 5-10% (v/v) methanol in dichloromethane to afford the title compound (free base) as a colourless oil. The free base was dissolved in diethyl ether (3 ml) and treated dropwise with 2 M hydrochloric acid in diethyl ether (1 ml). The resulting precipitate was collected by filtration, washed with diethyl ether (15 ml) and dried under reduced pressure to afford the title compound (1:1 hydrochloric acid salt) as a colourless solid (0.13 g, 0.31 mmol). 1H NMR (400 MHz, CD3OD) δH 1.04 (2H, brq, J 9.0), 1.11-1.25 (3H, m), 1.44 (6H, d, J 7.0), 1.54 (2H, br d, J 13.0), 1.62-1.90 (4H, m), 3.33-3.42 (4H, m), 3.95 (3H, s), 4.26 (2H, d, J 7.0), 4.74-4.86 (2H, m), 6.76 (1H, d, J 7.5), 7.09 (1H, t, J 8.0), 7.21 (1H, d, J 7.5), 7.46 (1H, s); EIMS: m/z 384.2 [M+H]+.

Workup

  1. extractionextracted into dichloromethane (2×30 ml)
  2. dry with materialThe combined organic layers were dried with magnesium sulfate
  3. customevaporated to an oil
  4. customThis was purified by flash chromatography
  5. washeluting with 5-10% (v/v) methanol in dichloromethane

Sources & evidence

ORD record
ord-78772f1302c341138fd73623613beb6b
Source dataset
uspto-grants-2007_12
Patent number
US07304064B2

Reaction notes

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