Diisopropylethylamine → 4,7-Difluoro-2-(2-iodo-3-methyl-benzoylamino)-indan-2-carboxylic acid ethyl ester

HRID 1047954Notes

Reaction equation

HRID 1047954 reaction equation
[I:1][C:2]1[C:10]([CH3:11])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.Cl.[CH2:13]([O:15][C:16]([C:18]1([NH2:29])[CH2:26][C:25]2[C:20](=[C:21]([F:28])[CH:22]=[CH:23][C:24]=2[F:27])[CH2:19]1)=[O:17])[CH3:14].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.CCOC(C)=O>[CH2:13]([O:15][C:16]([C:18]1([NH:29][C:4](=[O:6])[C:3]2[CH:7]=[CH:8][CH:9]=[C:10]([CH3:11])[C:2]=2[I:1])[CH2:26][C:25]2[C:20](=[C:21]([F:28])[CH:22]=[CH:23][C:24]=2[F:27])[CH2:19]1)=[O:17])[CH3:14]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 27593652-Iodo-3-methylbenzoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 685909942-Amino-4,7-difluoro-indan-2-carboxylic acid ethyl ester HCl salt

Product 1

HCID 593142174,7-Difluoro-2-(2-iodo-3-methyl-benzoylamino)-indan-2-carboxylic acid ethyl esterYield 75.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-iodo-3-methyl-benzoic acid (1.31 g, 5 mmol), 2-amino-4,7-difluoro-indan-2-carboxylic acid ethyl ester HCl salt (1.38 g, 5 mmol), HATU [O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium PF6, 3.80 g, 10 mmol) in anhydrous DMF (20 mL) is added DIPEA (N,N-diisopropylethylamine, 3.3 mL, 15 mmol). The resulting solution is stirred at RT for two days. After the removal of DMF in vacuo, the residue obtained is dissolved in EtOAc (200 mL) and washed with saturated NaHCO3 (1×100 mL) and brine (2×100 mL). The organic layer is dried over anhydrous Na2SO4 and concentrated in vacuo. The obtained residue is purified by flash column chromatography (40 g silica gel, gradient elution: 0%-50% EtOAc in heptane) to give a pure product (390) as white solid (1.83 g, 75%).

Workup

  1. customAfter the removal of DMF in vacuo
  2. customthe residue obtained
  3. washwashed with saturated NaHCO3 (1×100 mL) and brine (2×100 mL)
  4. dry with materialThe organic layer is dried over anhydrous Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe obtained residue is purified by flash column chromatography (40 g silica gel, gradient elution: 0%-50% EtOAc in heptane)

Sources & evidence

ORD record
ord-8f114674b86d4428851ed166c0df24a5
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Reaction notes

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