Diisopropylethylamine → 5-(2-Ethoxycarbonyl-indan-2-ylcarbamoyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

HRID 1047726Notes

Reaction equation

HRID 1047726 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:14]([C:18](O)=[O:19])=[CH:13][CH:12]=[CH:11][C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:21]([O:23][C:24]([C:26]1([NH2:35])[CH2:34][C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH2:27]1)=[O:25])[CH3:22].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][C:14]=2[C:18](=[O:19])[NH:35][C:26]2([C:24]([O:23][CH2:21][CH3:22])=[O:25])[CH2:34][C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH2:27]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10921653Ethyl 2-amino-2,3-dihydro-1H-indene-2-carboxylateHCID 221852932-BOC-1,2,3,4-Tetrahydroisoquinoline-5-carboxylic acid

Product 1

HCID 593143145-(2-Ethoxycarbonyl-indan-2-ylcarbamoyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl esterYield 30.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3,4-dihydro-1H-isoquinoline-2,5-dicarboxylic acid 2-tert-butyl ester (2 g, 7.2 mmol), 2-amino-indan-2-carboxylic acid ethyl ester (1.5 g, 7.2 mmol), HATU (3.27 g, 8.6 mmol) in anhydrous DMF (20 mL) is added DIPEA (1.42 mL, 8.6 mmol). The resulting solution is stirred at RT overnight. After the removal of DMF in vacuo, the residue is dissolved in EtOAc (150 mL) and washed with water (1×20 mL) and brine (2×20 mL). The organic layer is dried over anhydrous Na2SO4 and concentrated in vacuo. The residue is purified by HPLC to give a pure product (71) as white solid (1.02 g, 30%).

Workup

  1. customAfter the removal of DMF in vacuo
  2. dissolutionthe residue is dissolved in EtOAc (150 mL)
  3. washwashed with water (1×20 mL) and brine (2×20 mL)
  4. dry with materialThe organic layer is dried over anhydrous Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified by HPLC

Sources & evidence

ORD record
ord-3bb3d161f6da4a2192dadcea6a0a0737
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Reaction notes

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