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

HRID 1433011Notes

Reaction equation

HRID 1433011 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([Cl:17])=[CH:14][CH:15]=2)[CH:10]=[C:9]1[CH2:18][N:19]1[CH2:24][C:23](=[O:25])[N:22]([CH2:26][C:27]2[CH:32]=[CH:31][C:30]([C:33]#[N:34])=[C:29]([N:35]=C(C3C=CC=CC=3)C3C=CC=CC=3)[CH:28]=2)[CH:21]([C:49]([O:51][CH3:52])=[O:50])[CH2:20]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>Cl.CO>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([Cl:17])=[CH:14][CH:15]=2)[CH:10]=[C:9]1[CH2:18][N:19]1[CH2:24][C:23](=[O:25])[N:22]([CH2:26][C:27]2[CH:32]=[CH:31][C:30]([C:33]#[N:34])=[C:29]([NH2:35])[CH:28]=2)[CH:21]([C:49]([O:51][CH3:52])=[O:50])[CH2:20]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 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 ester

Product 1

HCID 54288444(+/-)-2-[4-(3-Amino-4-cyano-benzyl)-3-methoxycarbonyl-5-oxo-piperazin-1-ylmethyl]-5-chloro-indole-1-carboxylic acid tert-butyl esterYield 95.3%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 887MethanolSolvent

Procedure

Partially-purified (±)-2-{4-[3-(benzhydrylidene-amino)-4-cyano-benzyl]-3-methoxycarbonyl-5-oxo-piperazin-1-ylmethyl}-5-chloro-indole-1-carboxylic acid tert-butyl ester (550 mg, 0.76 mmol) is suspended in reagent grade MeOH (20 mL). To the heterogeneous mixture is added 12M HCl (5 drops) and the reaction mixture is maintained at ambient temperature until homogeneous (˜30 min). The reaction mixture is partitioned between diethyl ether and water containing excess NaHCO3 (500 mL). The layers are separated and the organic phase is washed with brine, dried over anhydrous Na2SO4, filtered and concentrated. The crude residue is chromatographed on silica gel (CH2Cl2 to 2% MeOH/CH2Cl2) to provide 400 mg (94%) of the title compound which is used directly in the next reaction. MS (ISP loop): 532 (M+H).

Workup

  1. customThe reaction mixture is partitioned between diethyl ether and water containing excess NaHCO3 (500 mL)
  2. customThe layers are separated
  3. washthe organic phase is washed with brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue is chromatographed on silica gel (CH2Cl2 to 2% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-ac3346133ff04282913c14d6a79d9305
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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