1,2-Dichloroethane → 7-{1-[1-(3,4-dimethoxy-benzoyl)-pyrrolidin-2-yl]-benzoylamino}-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester

HRID 1524296Notes

Reaction equation

HRID 1524296 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH3:13])[C:6]([OH:8])=O.C(Cl)CCl.[CH:18]1[CH:19]=CC2N(O)N=[N:24][C:22]=2[CH:23]=1.CCN(CC)CC.Cl.[CH2:36]([O:43][C:44]([N:46]1[CH2:55][CH2:54][C:53]2[C:48](=[CH:49][C:50]([NH:56][C:57](=[O:69])[C:58]3[CH:63]=[CH:62][CH:61]=[C:60](C4CCCN4)[CH:59]=3)=[CH:51][CH:52]=2)[CH2:47]1)=[O:45])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>CN(C=O)C>[CH2:36]([O:43][C:44]([N:46]1[CH2:55][CH2:54][C:53]2[C:48](=[CH:49][C:50]([NH:56][C:57](=[O:69])[C:58]3([CH:19]4[CH2:18][CH2:23][CH2:22][N:24]4[C:6](=[O:8])[C:5]4[CH:9]=[CH:10][C:11]([O:12][CH3:13])=[C:3]([O:2][CH3:1])[CH:4]=4)[CH:59]=[CH:60][CH:61]=[CH:62][CH2:63]3)=[CH:51][CH:52]=2)[CH2:47]1)=[O:45])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 7121Veratric AcidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 666549657-(3-pyrrolidin-2-yl-benzoylamino)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester HCl

Product 1

HCID 680893827-{1-[1-(3,4-dimethoxy-benzoyl)-pyrrolidin-2-yl]-benzoylamino}-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl esterYield 57.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Stir a solution of 3,4-dimethoxybenzoic acid (85 mg, 0.461 mmol), EDC (91 mg, 0.461 mmol), HOBt (66 mg, 0.461 mmol), and Et3N (0.195 mL, 1.383 mmol) in DMF (7 mL) at room temperature for 30 min. To this add 7-(3-pyrrolidin-2-ylbenzoylamino)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester HCl salt (236 mg, 0.384 mmol) as a solution in DMF and stir the reaction at room temperature for 48 h. Quench the reaction with sat. NH4Cl (100 mL) and extract with EtOAc (2×150 mL). Wash the organic layers with water (100 mL) then dry (Na2SO4) and concentrate to an oil. Purify by silica gel chromatography eluting with 10% EtOAc/hexane to 100% EtOAc. Concentrate the fractions containing product in vacuo to afford 137 mg of 7-{1-[1-(3,4-dimethoxy-benzoyl)-pyrrolidin-2-yl]-benzoylamino}-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester as a solid foam.

Workup

  1. customthe reaction at room temperature for 48 h
  2. customQuench
  3. customthe reaction with sat. NH4Cl (100 mL)
  4. extractionextract with EtOAc (2×150 mL)
  5. washWash the organic layers with water (100 mL)
  6. dry with materialthen dry (Na2SO4)
  7. concentrationconcentrate to an oil
  8. customPurify by silica gel chromatography
  9. washeluting with 10% EtOAc/hexane to 100% EtOAc
  10. concentrationConcentrate the fractions
  11. additioncontaining product in vacuo

Sources & evidence

ORD record
ord-494eb01d0f6e4661bbe6fe8787aabced
Source dataset
uspto-grants-2015_07
Patent number
US09079880B2

Reaction notes

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