Diisopropylethylamine → 8-(2-Ethoxycarbonyl-indan-2-ylcarbamoyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

HRID 1047838Notes

Reaction equation

HRID 1047838 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[C:11]([C:18](O)=[O:19])[CH:12]=[CH:13][CH:14]=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](=[C:11]([C:18](=[O:19])[NH:35][C:26]3([C:24]([O:23][CH2:21][CH3:22])=[O:25])[CH2:34][C:33]4[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=4)[CH2:27]3)[CH:12]=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

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 450740022-[(Tert-butoxy)carbonyl]-1,2,3,4-tetrahydroisoquinoline-8-carboxylic acid

Product 1

HCID 593142148-(2-Ethoxycarbonyl-indan-2-ylcarbamoyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl esterYield 99%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3,4-dihydro-1H-isoquinoline-2,8-dicarboxylic acid 2-tert-butyl ester (2.0 g, 7.2 mmol), 2-amino-indan-2-carboxylic acid ethyl ester (1.5 g, 7.2 mmol), HATU (3.3 g, 8.6 mmol) in anhydrous DMF (70 mL) is added DIPEA (1.4 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 (1×10 mL) and brine (2×10 mL). The organic layer is dried over anhydrous Na2SO4 and concentrated in vacuo. The residue is purified by flash column chromatography (200 g silica gel, gradient elution: 5-50% EtOAc in heptane) to give a pure product (217) as white solid (3.3 g, 99%).

Workup

  1. customAfter the removal of DMF in vacuo
  2. dissolutionthe residue is dissolved in EtOAc (150 mL)
  3. washwashed with water (1×10 mL) and brine (2×10 mL)
  4. dry with materialThe organic layer is dried over anhydrous Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified by flash column chromatography (200 g silica gel, gradient elution: 5-50% EtOAc in heptane)

Sources & evidence

ORD record
ord-0b3154918832476faa53eea71894971f
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Reaction notes

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