Diisopropylethylamine → 5-Cyano-2-(2-isopropoxy-3-methyl-benzoylamino)-indan-2-carboxylic acid ethyl ester

HRID 1047757Notes

Reaction equation

HRID 1047757 reaction equation
[CH:1]([O:4][C:5]1[C:13]([CH3:14])=[CH:12][CH:11]=[CH:10][C:6]=1[C:7]([OH:9])=O)([CH3:3])[CH3:2].[CH2:15]([O:17][C:18]([C:20]1([NH2:31])[CH2:28][C:27]2[C:22](=[CH:23][CH:24]=[C:25]([C:29]#[N:30])[CH:26]=2)[CH2:21]1)=[O:19])[CH3:16].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>[CH2:15]([O:17][C:18]([C:20]1([NH:31][C:7](=[O:9])[C:6]2[CH:10]=[CH:11][CH:12]=[C:13]([CH3:14])[C:5]=2[O:4][CH:1]([CH3:2])[CH3:3])[CH2:28][C:27]2[C:22](=[CH:23][CH:24]=[C:25]([C:29]#[N:30])[CH:26]=2)[CH2:21]1)=[O:19])[CH3:16]

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 593140882-Isopropoxy-3-methyl-benzoic acidHCID 593141522-Amino-5-cyano-indan-2-carboxylic acid ethyl ester

Product 1

HCID 593143585-Cyano-2-(2-isopropoxy-3-methyl-benzoylamino)-indan-2-carboxylic acid ethyl esterYield 86.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-isopropoxy-3-methyl-benzoic acid (377 mg, 1.94 mmol), 2-amino-5-cyano-indan-2-carboxylic acid ethyl ester (670 mg, 2.91 mmol), HATU (1.11 g, 2.91 mmol) in anhydrous DMF (15 mL) is added DIPEA (480 μL, 2.91 mmol). The resulting solution is stirred at RT overnight. After the removal of DMF in vacuo, the residue is dissolved in EtOAc (100 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 (120 g silica gel, gradient elution: 5%-70% EtOAc in heptane) to give a pure product (110) as a white semisolid (680 mg, 86%).

Workup

  1. customAfter the removal of DMF in vacuo
  2. dissolutionthe residue is dissolved in EtOAc (100 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 (120 g silica gel, gradient elution: 5%-70% EtOAc in heptane)

Sources & evidence

ORD record
ord-23632c188be8436687b74a81fa8d632e
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Reaction notes

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