1,2-Dichloroethane → 7-[3-(1-tert-butoxycarbonyl-pyrrolidin-2-yl)-benzoylamino]-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester

HRID 1524294Notes

Reaction equation

HRID 1524294 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([C:19](O)=[O:20])[CH:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(CC)CC.[CH2:43]([O:50][C:51]([N:53]1[CH2:62][CH2:61][C:60]2[C:55](=[CH:56][C:57]([NH2:63])=[CH:58][CH:59]=2)[CH2:54]1)=[O:52])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>CN(C=O)C.CCOC(C)=O>[CH2:43]([O:50][C:51]([N:53]1[CH2:62][CH2:61][C:60]2[C:55](=[CH:56][C:57]([NH:63][C:19](=[O:20])[C:15]3[CH:16]=[CH:17][CH:18]=[C:13]([CH:9]4[CH2:10][CH2:11][CH2:12][N:8]4[C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[CH:14]=3)=[CH:58][CH:59]=2)[CH2:54]1)=[O:52])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 450739843-{1-[(Tert-butoxy)carbonyl]pyrrolidin-2-yl}benzoic acidHCID 53419255Benzyl 7-amino-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 666551417-[3-(1-tert-butoxycarbonyl-pyrrolidin-2-yl)-benzoylamino]-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl esterYield 96.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-(3-carboxy-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (500 mg, 1.682 mmol), EDC (346 mg, 1.766 mmol), and HOBt (240 mg, 1.682 mmol) in DMF (5 mL) add Et3N (0.355 mL, 2.523 mmol) and stir the solution at room temperature for 15 min. To this add a solution of the 7-amino-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester (500 mg, 1.682 mmol) as a solution in DMF (5 mL) and stir the solution at 65° C. for 24 h. Dilute the reaction with EtOAc (250 mL) and wash with sat. NH4Cl (250 mL), sat. NaHCO3 (250 mL), then water (250 mL). Extract the aqueous layers with more EtOAc (250 mL) and dry the combined organics (Na2SO4), and concentrate in vacuo to give 902 mg of 7-[3-(1-tert-butoxycarbonyl-pyrrolidin-2-yl)-benzoylamino]-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester as a solid.

Workup

  1. stirringstir the solution at 65° C. for 24 h
  2. additionDilute
  3. washwash with sat. NH4Cl (250 mL), sat. NaHCO3 (250 mL)
  4. extractionExtract the aqueous layers with more EtOAc (250 mL)
  5. dry with materialdry the combined organics (Na2SO4)
  6. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-2bf05f732927415cbfc8c38130750f9d
Source dataset
uspto-grants-2015_07
Patent number
US09079880B2

Reaction notes

Loading…