1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2,5-dioxopyrrolidin-1-yl 5-(2,4-difluorophenoxy)-1-isobutyl-1H-indazole-6-carboxylate

HRID 912447Notes

Reaction equation

HRID 912447 reaction equation
[F:1][C:2]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:3]=1[O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][C:13]=1[C:14]([OH:16])=[O:15])[N:10]([CH2:17][CH:18]([CH3:20])[CH3:19])[N:9]=[CH:8]2.O[N:27]1[C:31](=[O:32])[CH2:30][CH2:29][C:28]1=[O:33].CCN=C=NCCCN(C)C>C(Cl)Cl>[O:33]=[C:28]1[CH2:29][CH2:30][C:31](=[O:32])[N:27]1[O:15][C:14]([C:13]1[CH:12]=[C:11]2[C:7]([CH:8]=[N:9][N:10]2[CH2:17][CH:18]([CH3:20])[CH3:19])=[CH:6][C:5]=1[O:4][C:3]1[CH:21]=[CH:22][C:23]([F:25])=[CH:24][C:2]=1[F:1])=[O:16]

Participants

5

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 80170N-HydroxysuccinimideHCID 574187635-(2,4-Difluorophenoxy)-1-isobutyl-1H-indazole-6-carboxylic acid

Product 1

HCID 426324812,5-dioxopyrrolidin-1-yl 5-(2,4-difluorophenoxy)-1-isobutyl-1H-indazole-6-carboxylateYield 81.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

5-(2,4-Difluorophenoxy)-1-isobutyl-1H-indazole-6-carboxylic acid (39.5 g, 113.9 mmol), N-hydroxysuccinimide (17.0 g, 148 mmol) and EDCI (26.0 g, 137 mmol) were dissolved in CH2Cl2 (200 mL). The solution was stirred for 3 hours and then was diluted with 100 mL CH2Cl2 and washed sequentially with a saturated NH4Cl solution, twice with a saturated Na2CO3 solution, and once with brine. The organics were dried (MgSO4), filtered, and concentrated under reduced pressure. The crude residue was precipitated from Et2O to afford 41.0 g of 5-(2,4-difluorophenoxy)-1-isobutyl-1H-indazole-6-carboxylic acid 2,5-dioxopyrrolidin-1-yl ester (81% yield). 1H NMR (400 MHz, CDCl3) δ 8.26 (s, 1H), 7.95 (s, 1H), 7.20 (s, 1H), 7.05-6.94 (m, 2H), 6.88-6.81 (m, 1H), 4.24 (d, J=7.83 Hz, 2H), 2.90 (s, 4H), 2.43-2.32 (m, 1H), 0.96 (d, J=7.04 Hz, 6H).

Workup

  1. washwashed sequentially with a saturated NH4Cl solution, twice with a saturated Na2CO3 solution
  2. dry with materialThe organics were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe crude residue was precipitated from Et2O

Sources & evidence

ORD record
ord-7e18da731a4c4d31982b487b7dc6ea2d
Source dataset
uspto-grants-2011_09
Patent number
US08026233B2

Reaction notes

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