1,2-Dichloroethane → N-{[7-(4-N-Boc-Piperazin-1-yl)-3,4-dihydro-1(1H)-isoquinolinone-2-yl]acetyl}-3(S)-(ethynyl)-beta-alanine ethyl ester

HRID 1377526Notes

Reaction equation

HRID 1377526 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:23]=[C:22]3[C:17]([CH2:18][CH2:19][N:20]([CH2:25][C:26](O)=[O:27])[C:21]3=[O:24])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.Cl.[CH2:44]([O:46][C:47](=[O:53])[CH2:48][C@@H:49]([C:51]#[CH:52])[NH2:50])[CH3:45].CCN(CC)CC>>[CH2:44]([O:46][C:47](=[O:53])[CH2:48][C@@H:49]([C:51]#[CH:52])[NH:50][C:26](=[O:27])[CH2:25][N:20]1[CH2:19][CH2:18][C:17]2[C:22](=[CH:23][C:14]([N:11]3[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:7])[CH2:13][CH2:12]3)=[CH:15][CH:16]=2)[C:21]1=[O:24])[CH3:45]

Participants

6

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 11794693[7-(4-t-Butoxycarbonylpiperazin-1-yl)-3,4-dihydro-1(1H)-isoquinolinone-2-yl]acetic acidHCID 86751219Ethyl (3s)-3-aminopent-4-ynoate hydrochloride

Product 1

HCID 86751218N-{[7-(4-N-Boc-Piperazin-1-yl)-3,4-dihydro-1(1H)-isoquinolinone-2-yl]acetyl}-3(S)-(ethynyl)-beta-alanine ethyl ester

Procedure

To a solution of 1-5 (150 mg, 0.39 mmol), HOBT (63 mg, 0.46 mmol) and EDC (111 mg, 0.58 mmol) was added 3(S)-(ethynyl)-β-alanine ethyl ester hydrochloride (1-32) (U.S. Pat. No. 5,272,162; 82 mg, 0.46 mmol) and Et3N (80.7 gl, 0.58 mmol). The mixture was stirred at room temperature under argon for 16 hours and then partitioned between EtOAc and 10% citric acid. The aqueous phase was extracted with EtOAc (x3) and the combined organic layers then washed with saturated aqueous NaHCO3 followed by brine. Removal of the dried (MgSO4) solvent afforded a yellow oil which was purified by column chromatography (silica gel; hexane/EtOAc 1:1) to give 1-33 as an oil. Rf (silica; EtOAc/hexane 2:1) 0.57 ##STR51##

Workup

  1. custompartitioned between EtOAc and 10% citric acid
  2. extractionThe aqueous phase was extracted with EtOAc (x3)
  3. washthe combined organic layers then washed with saturated aqueous NaHCO3
  4. customRemoval of the
  5. dry with materialdried (MgSO4) solvent
  6. customafforded a yellow oil which
  7. customwas purified by column chromatography (silica gel; hexane/EtOAc 1:1)

Sources & evidence

ORD record
ord-c36e48a642a54f209e6ce7c3eff7d424
Source dataset
uspto-grants-1997_09
Patent number
US05665723

Reaction notes

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