Diisopropylethylamine → 2-[(6-Fluoro-4H-benzo[1,3]dioxine-8-carbonyl)-amino]-indan-2-carboxylic acid ethyl ester

HRID 1047716

Reaction equation

HRID 1047716 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:12]([OH:14])=O)[C:5]2[O:10][CH2:9][O:8][CH2:7][C:6]=2[CH:11]=1.[CH2:15]([O:17][C:18]([C:20]1([NH2:29])[CH2:28][C:27]2[C:22](=[CH:23][CH:24]=[CH:25][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:29][C:12]([C:4]2[C:5]3[O:10][CH2:9][O:8][CH2:7][C:6]=3[CH:11]=[C:2]([F:1])[CH:3]=2)=[O:14])[CH2:28][C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH2:21]1)=[O:19])[CH3:16]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27799016-fluoro-4H-1,3-benzodioxine-8-carboxylic acidHCID 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-carboxylate

Product 1

HCID 593143692-[(6-Fluoro-4H-benzo[1,3]dioxine-8-carbonyl)-amino]-indan-2-carboxylic acid ethyl esterYield 95.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-fluoro-4H-benzo[1,3]dioxine-8-carboxylic acid (386 mg, 1.95 mmol), 2-amino-indan-2-carboxylic acid ethyl ester (400 mg, 1.95 mmol), HATU (1.11 g, 2.93 mmol) in anhydrous DMF (8 mL) is added DIPEA (484 μL, 2.93 mmol). The resulting solution is stirred at RT overnight. After the removal of DMF in vacuo, the residue is dissolved in EtOAc (70 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: 5-50% EtOAc in heptane) to give a pure product (61) as white solid (720 mg, 6%).

Workup

  1. customAfter the removal of DMF in vacuo
  2. dissolutionthe residue is dissolved in EtOAc (70 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: 5-50% EtOAc in heptane)

Sources & evidence

ORD record
ord-907077d88b874d6785d4f002d9a8ecda
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Linked notes

Loading…