1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 57920019, compound

HRID 19348Notes

Reaction equation

HRID 19348 reaction equation
[Cl:1][C:2]1[CH:25]=[CH:24][CH:23]=[CH:22][C:3]=1[O:4][C:5]1[CH2:9][N:8]([CH:10]([CH2:14][CH:15]([CH3:20])[C:16]([F:19])([F:18])[F:17])[C:11]([OH:13])=O)[C:7](=[O:21])[CH:6]=1.[CH3:26]N(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.Cl.[OH:48][C@@H:49]([CH2:79]O)[CH2:50][N:51]1[CH:55]=[CH:54][C:53]([NH:56]C(=O)[C@@H](N2CC(OC3C=CC=C(Cl)C=3Cl)=CC2=O)CC(C)C)=[N:52]1>ClCCl>[OH:48][C:49]([CH3:79])([CH3:26])[CH2:50][N:51]1[CH:55]=[CH:54][C:53]([NH:56][C:11](=[O:13])[CH:10]([N:8]2[CH2:9][C:5]([O:4][C:3]3[CH:22]=[CH:23][CH:24]=[CH:25][C:2]=3[Cl:1])=[CH:6][C:7]2=[O:21])[CH2:14][CH:15]([CH3:20])[C:16]([F:17])([F:18])[F:19])=[N:52]1

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 668951522-[4-(2-Chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-5,5,5-trifluoro-4-methyl-pentanoic acidHCID 66899094HMS5552 HCl

Product 1

HCID 57920019HCID 57920019, compoundYield 59%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

In a round bottom flask under argon was placed 2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-5,5,5-trifluoro-4-methyl-pentanoic acid (575 mg, 1.52 mmol) in dichloromethane (25 mL). To this mixture was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (296 μL, 1.67 mmol) and 1-hydoxybenzotriazole (216 mg, 1.59 mmol) and stirred at 25° C. for 2 h. After this time, 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in US20080021032, Example 80, 283 mg, 1.83 mmol) was added and the mixture stirred for 16 h at 25° C. After this time, the mixture was diluted with dichloromethane (10 mL) and washed with a 1N aqueous hydrochloric acid solution (10 mL), water (10 mL) and a saturated aqueous sodium bicarbonate solution (10 mL) dried over magnesium sulfate, filtered and concentrated in vacuo. Purification by AnaLogix IntelliFlash flash chromatography (12 g column, 20% ethyl acetate/hexanes to 80% ethyl acetate/hexanes) afforded 2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-5,5,5-trifluoro-4-methyl-pentanoic acid [1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-amide (460 mg, 59%) as a yellow foam: HR-ES-MS m/z calculated for C23H26N4O4ClF3 [M+H]+ 515.1668, observed 515.1664; 1H NMR (300 MHz, CDCl3) δ ppm 1.15 (s, 3H), 1.16 (s, 3H), 1.20 (d, J=6.6 Hz, 3H), 1.89-2.19 (m, 2H), 2.30 (m, 1H), 3.94 (s, 2H), 4.28 (m, 1H), 4.31 (m, 1H), 4.90, 4.91 (2×s, 1H), 5.00 (dd, J=4.8, 10.9 Hz, 1H), 6.68 (br. s., 1H), 7.20-7.37 (m, 4H), 7.49 (d, J=7.9 Hz, 1H), 8.65, 8.89 (2×br. s., 1H).

Workup

  1. customIn a round bottom flask under argon was placed
  2. stirringthe mixture stirred for 16 h at 25° C
  3. washwashed with a 1N aqueous hydrochloric acid solution (10 mL), water (10 mL)
  4. dry with materiala saturated aqueous sodium bicarbonate solution (10 mL) dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by AnaLogix IntelliFlash flash chromatography (12 g column, 20% ethyl acetate/hexanes to 80% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-0edb23b09e6041359c9bed514eddbaac
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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