Dichloromethane → 2-[(2,5-Dichloro-pyridine-3-carbonyl)-amino]-indan-2-carboxylic acid ethyl ester

HRID 1047933Notes

Reaction equation

HRID 1047933 reaction equation
[CH2:1]([O:3][C:4]([C:6]1([NH2:15])[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7]1)=[O:5])[CH3:2].C(Cl)Cl.CCN(C(C)C)C(C)C.[Cl:28][C:29]1[C:34]([C:35](Cl)=[O:36])=[CH:33][C:32]([Cl:38])=[CH:31][N:30]=1>CN(C1C=CN=CC=1)C.CC(O)C.C(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1([NH:15][C:35]([C:34]2[C:29]([Cl:28])=[N:30][CH:31]=[C:32]([Cl:38])[CH:33]=2)=[O:36])[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7]1)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 81531DiisopropylethylamineHCID 27999962,5-Dichloro-nicotinoyl chlorideHCID 10921653Ethyl 2-amino-2,3-dihydro-1H-indene-2-carboxylate

Product 1

HCID 593142262-[(2,5-Dichloro-pyridine-3-carbonyl)-amino]-indan-2-carboxylic acid ethyl esterYield 107.7%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 21966342Isopropanol methylene chlorideSolvent

Procedure

A 30 mL reaction vial is charged with 2-aminoindan-2-carboxylic acid ethyl ester (1 g, 4.87 mmol) and dry DCM (5 mL). A stirring bar is added and stirring is initiated. DIPEA (1.35 mL, 7.8 mmol) is added. 2,5-dichloro-pyridine-3-carbonyl chloride (1.23 g, 5.85 mmol) and DMAP (8 mg, cat.) are added. The reaction is capped. After 57 days, tlc analysis (silica, 10% iPrOH/DCM) indicates that the starting has been completely consumed. The contents of the reaction flask are transferred to a separatory funnel and diluted with EtOAc (60 mL). This is washed with water (2×25 mL), saturated aqueous NaHCO3 (2×25 mL), and brine (25 mL), and then dried over MgSO4, filtered and evaporated by pumping to constant weight yields 1.99 g of off-white solid. This is diluted with DCM (20 mL) and applied to a silica column ((80 g) on an ISCO Companion. The column is eluted with 5% EtOAc in heptanes for 3 column volumes followed by a linear gradient to 75% EtOAc in heptanes over 12 column volumes. 17 mL fractions of UV positive eluent are collected. Fraction 12-16 are combined and evaporated by pumping to constant weight to give light yellow solid (1.39 g, 75%).

Workup

  1. customA 30 mL reaction
  2. additionA stirring bar is added
  3. customThe reaction is capped
  4. customhas been completely consumed
  5. customThe contents of the reaction flask are transferred to a separatory funnel
  6. additiondiluted with EtOAc (60 mL)
  7. washThis is washed with water (2×25 mL), saturated aqueous NaHCO3 (2×25 mL), and brine (25 mL)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customevaporated

Sources & evidence

ORD record
ord-404fd16f4dcd45a999ce204fb9428988
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Reaction notes

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