1,2-Dichloroethane → HCID 69410668, compound

HRID 1592778Notes

Reaction equation

HRID 1592778 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH:17]([CH2:18][N:19]([CH3:32])[CH:20]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=2)[C:21]([O-])=[O:22])[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li+].Cl.Cl.[N:36]1([CH2:41][C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=2[N:48]2[CH2:53][CH2:52][NH:51][CH2:50][CH2:49]2)[CH2:40][CH2:39][CH2:38][CH2:37]1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH:17]([CH2:18][N:19]([CH:20]([CH2:24][C:25]2[CH:26]=[CH:27][C:28]([Cl:31])=[CH:29][CH:30]=2)[C:21](=[O:22])[N:51]2[CH2:50][CH2:49][N:48]([C:43]3[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=3[CH2:41][N:36]3[CH2:37][CH2:38][CH2:39][CH2:40]3)[CH2:53][CH2:52]2)[CH3:32])[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 17952276HCID 17952276, compoundHCID 23667319HCID 23667319, compound

Product 1

HCID 69410668HCID 69410668, compoundYield 17.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Lithium 2-[(2-tert-butoxycarbonyl-1,2,3,4-tetrahydro-isoquinolin-3-ylmethyl)-methyl-amino]-3-(4-chloro-phenyl)-propionate (0.59 gm, 1.27 mmol), the compound of Step A (0.27 gm, 0.85 mmol), EDC (0.24 gm, 1.27 mmol) and HOBt (0.17 gm, 1.27 mmol) were combined and dissolved in anhydrous DMF (5 mL). DIPEA was added (440 microliter, 2.54 mmol), and the reaction was stirred under nitrogen overnight at room temperature. The reaction was concentrated and reconstituted in CH2Cl2 and then diluted with NaHCO3. After separation of the organic phase, the aqueous layer was extracted with CH2Cl2 (2×). The combined organics were dried (Na2SO4), filtered and concentrated. Chromatography (EtOAc to 5% MeOH/EtOAc) gave about 100 mg of 3-[({1-(4-Chloro-benzyl)-2-oxo-2-[4-(2-pyrrolidin-1-ylmethyl-phenyl)-piperazin-1-yl]-ethyl}-methyl-amino)-methyl]-3,4-dihydro-1H-isoquinoline-2-carboxylic acid t-butyl ester. MS (m/z, ES+): 686.4.

Workup

  1. concentrationThe reaction was concentrated
  2. additiondiluted with NaHCO3
  3. customAfter separation of the organic phase
  4. extractionthe aqueous layer was extracted with CH2Cl2 (2×)
  5. dry with materialThe combined organics were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-b7e56b34782a4bcbbda240a9de89b60a
Source dataset
uspto-grants-2007_11
Patent number
US07291619B2

Reaction notes

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