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

HRID 909206Notes

Reaction equation

HRID 909206 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.CCN=C=NCCCN(C)C.O[N:38]1[C:42](=[O:43])[CH2:41][CH2:40][C:39]1=[O:44]>ClCCl>[O:44]=[C:39]1[CH2:40][CH2:41][C:42](=[O:43])[N:38]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-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

5-(2,4-Difluorophenoxy)-1-isobutyl-1H-indazole-6-carboxylic acid (17d; prepared according to Example 110) (25.0 g, 72.2 mmol), EDCI (18.0 g, 93.8 mmol), and 1-hydroxypyrrolidine-2,5-dione (9.97 g, 86.6 mmol) were suspended in dichloromethane and stirred at room temperature for 2 hours. The mixture was diluted with dichloromethane (500 mL) and washed with saturated NH4Cl (2×200 mL), saturated NaHCO3 (2×200 mL) and brine (200 mL). The organics were dried over MgSO4 and concentrated under reduced pressure to afford the crude product as yellow foam.

Workup

  1. washwashed with saturated NH4Cl (2×200 mL), saturated NaHCO3 (2×200 mL) and brine (200 mL)
  2. dry with materialThe organics were dried over MgSO4
  3. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-9ecf229ab1e74a2f92a8d7d120335bc0
Source dataset
uspto-grants-2011_09
Patent number
US08017641B2

Reaction notes

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