2,2-Dimethylsuccinic acid → HCID 46223698, compound

HRID 1645364Notes

Reaction equation

HRID 1645364 reaction equation
C([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21]([C:23]3[NH:24][C:25]4[C:30]([C:31]=3[CH3:32])=[CH:29][CH:28]=[CH:27][C:26]=4[O:33][CH3:34])=[O:22])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.[CH3:35][C:36]([CH3:44])([CH2:40]C(O)=O)[C:37]([OH:39])=[O:38].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>C(O)(C(F)(F)F)=O.C(Cl)Cl.C(N(C(C)C)CC)(C)C.ClCCl>[CH3:34][O:33][C:26]1[CH:27]=[CH:28][CH:29]=[C:30]2[C:25]=1[NH:24][C:23]([C:21]([NH:20][C:17]1[CH:16]=[CH:15][C:14]([N:11]3[CH2:10][CH2:9][N:8]([C:6](=[O:5])[CH2:35][C:36]([CH3:44])([CH3:40])[C:37]([OH:39])=[O:38])[CH2:13][CH2:12]3)=[CH:19][CH:18]=1)=[O:22])=[C:31]2[CH3:32]

Participants

8

Reactant 4

HCID 117012,2-Dimethylsuccinic acidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 593651564-{4-[(7-methoxy-3-methyl-1H-indole-2-carbonyl)-amino]-phenyl}-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 46223698HCID 46223698, compoundYield 4.7%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 81531DiisopropylethylamineSolventHCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Procedure

4-{4-[(7-Methoxy-3-methyl-1H-indole-2-carbonyl)-amino]-phenyl}-piperazine-1-carboxylic acid tert-butyl ester (139 mg, 0.3 mmol) (see example 1) was stirred in 5 mL of 1:3 TFA/CH2Cl2 at r.t. overnight, then concentrated. The residue was dissolved in 5 mL of 30:70 diisopropylethylamine/anhydrous dichloromethane, 2,2-dimethyl-succinic acid (72 mg, 0.49 mmol), N-hydroxybenzotriazole (61 mg, 0.45 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (86 mg, 0.45 mmol) were added. The reaction mixture was stirred at room temperature overnight. After the reaction, solvent was evaporated. The resulted mixture was mixed with water and extracted with ethyl acetate twice. The organic layers were collected, combined, washed with brine before dried over sodium sulfate, and then concentrated to give a solid. The crude product was purified by reverse phase HPLC (10%-80% acetonitrile in water) to gave 7 mg of 4-(4-{4-[(7-methoxy-3-methyl-1H-indole-2-carbonyl)-amino]-phenyl}-piperazin-1-yl)-2,2-dimethyl-4-oxo-butyric acid. LCMS calcd for C27H32N4O5 (m/e) 492, obsd 493 (M+H).

Workup

  1. concentrationconcentrated
  2. additionwere added
  3. customAfter the reaction, solvent
  4. customwas evaporated
  5. additionThe resulted mixture was mixed with water
  6. extractionextracted with ethyl acetate twice
  7. customThe organic layers were collected
  8. washwashed with brine
  9. dry with materialbefore dried over sodium sulfate
  10. concentrationconcentrated
  11. customto give a solid
  12. customThe crude product was purified by reverse phase HPLC (10%-80% acetonitrile in water)

Sources & evidence

ORD record
ord-0160d0c0cd7f40d2b89e1fb25a502b40
Source dataset
uspto-grants-2012_02
Patent number
US08124766B2

Reaction notes

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