Potassium Carbonate → (+/-)-2-{4-[3-(Benzhydrylidene-amino)-4-cyano-benzyl]-3-methoxycarbonyl-5-oxo-piperazin-1-ylmethyl}-5-chloro-indole-1-carboxylic acid tert-butyl ester

HRID 1433010Notes

Reaction equation

HRID 1433010 reaction equation
[CH3:1][O:2][C:3]([CH:5]1[CH2:10][NH:9][CH2:8][C:7](=[O:11])[N:6]1[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]#[N:20])=[C:15]([N:21]=[C:22]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:14]=1)=[O:4].C([O-])([O-])=O.[K+].[K+].[C:41]([O:45][C:46]([N:48]1[C:56]2[C:51](=[CH:52][C:53]([Cl:57])=[CH:54][CH:55]=2)[CH:50]=[C:49]1[CH2:58]Br)=[O:47])([CH3:44])([CH3:43])[CH3:42]>CC#N.C(OCC)C.O>[C:41]([O:45][C:46]([N:48]1[C:56]2[C:51](=[CH:52][C:53]([Cl:57])=[CH:54][CH:55]=2)[CH:50]=[C:49]1[CH2:58][N:9]1[CH2:8][C:7](=[O:11])[N:6]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]#[N:20])=[C:15]([N:21]=[C:22]([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)[C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH:14]=2)[CH:5]([C:3]([O:2][CH3:1])=[O:4])[CH2:10]1)=[O:47])([CH3:44])([CH3:43])[CH3:42]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 217084992-Bromomethyl-1-tert-butoxycarbonyl-5-chloroindoleHCID 54153171(+/-)-1-[3-(Benzhydrylidene-amino)-4-cyano-benzyl]-6-oxo-piperazine-2-carboxylic acid methyl ester

Product 1

HCID 86760983(+/-)-2-{4-[3-(Benzhydrylidene-amino)-4-cyano-benzyl]-3-methoxycarbonyl-5-oxo-piperazin-1-ylmethyl}-5-chloro-indole-1-carboxylic acid tert-butyl esterYield 55.2%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 21584184Diethylether waterSolvent

Procedure

To a mixture of (±)-1-[3-(benzhydrylidene-amino)-4-cyano-benzyl]-6-oxo-piperazine-2-carboxylic acid methyl ester (630 mg, 1.39 mmol) and K2CO3 (380 mg, 2.78 mmol) in anhydrous CH3CN (5 mL) at 0° C. is added 2-bromomethyl-5-chloro-indole-1-carboxylic acid tert-butyl ester (720 mg, 2.09 mmol), EXAMPLE 21, in CH3CN (4 mL). The reaction mixture is allowed to warm to ambient temperature then maintained for 16 hours. The reaction mixture is diluted with diethyl ether/water and the layers are separated. The organic phase is washed twice with water, brine, dried over anhydrous Na2SO4, filtered and concentrated. The crude residue is chromatographed on silica (CH2Cl2 to 2% MeOH/CH2Cl2) to provide 550 mg (55%) of the title compound which is used directly in the next reaction without further characterization.

Workup

  1. temperaturethen maintained for 16 hours
  2. customthe layers are separated
  3. washThe organic phase is washed twice with water, brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue is chromatographed on silica (CH2Cl2 to 2% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-03ca7cbe9bb447aa9a2c1ec0333e0ad6
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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