1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 57920118, compound

HRID 19186Notes

Reaction equation

HRID 19186 reaction equation
[OH:1][C@@H:2]([CH2:34]O)[CH2:3][N:4]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:33])[CH:11]([N:17]2[CH2:21][C:20]([O:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH3:30])[C:24]=3[Cl:31])=[CH:19][C:18]2=[O:32])[CH2:12][C:13]([F:16])([CH3:15])[CH3:14])=[N:5]1.[CH3:36]N(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.Cl.O[C@@H](CO)CN1C=CC(NC(=O)[C@@H](N2CC(OC3C=CC=C(Cl)C=3Cl)=CC2=O)CC(C)C)=N1>ClCCl>[OH:1][C:2]([CH3:34])([CH3:36])[CH2:3][N:4]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:33])[CH:11]([N:17]2[CH2:21][C:20]([O:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH3:30])[C:24]=3[Cl:31])=[CH:19][C:18]2=[O:32])[CH2:12][C:13]([F:16])([CH3:14])[CH3:15])=[N:5]1

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 579200982-[4-(2-Chloro-3-methoxyphenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-fluoro-4-methyl-pentanoic acid-[1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-amideHCID 66899094HMS5552 HCl

Product 1

HCID 57920118HCID 57920118, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

A solution of 2-[4-(2-chloro-3-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-fluoro-4-methyl-pentanoic acid (prepared as in Example 170, 200 mg, 0.54 mmol) in dichloromethane (20 mL) was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (92 mg, 0.59 mmol), 1-hydroxybenzotriazole (76 mg, 0.57 mmol) and 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032 Example 80, 100 mg, 0.65 mmol). The reaction mixture was stirred for 18 h at 25° C., under nitrogen and then diluted with dichloromethane, washed with 2N hydrochloric acid, saturated sodium bicarbonate solution, a saturated sodium chloride solution and dried over magnesium sulfate. The crude product obtained after concentration, was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 12 g; 0% to 10% methanol/dichloromethane) to afford 2-[4-(2-chloro-3-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-fluoro-4-methyl-pentanoic acid [1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-amide (156 mg, 57%) as a white powder: LR-ES-MS m/z calculated for C24H30ClFN4O5 [M]+ 508, observed 509 [M+H]+; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.05 (br. s., 3H), 1.06 (br. s., 3H), 1.19, 1.32 (2×d, J=3.0 Hz, 3H), 1.26, 1.39 (2×d, J=3.0 Hz, 3H), 1.96-2.33 (m, 2H), 3.90 (br. s., 5H), 4.25 (d, J=18.4 Hz, 1H), 4.52 (d, J=18.4 Hz, 1H), 4.67 (s, 1H), 4.77, 4.80 (2×s, 1H), 5.01, 5.10 (2×dd, J=9.8, 4.4 Hz, 1H), 6.44 (d, J=1.8 Hz, 1H), 7.00, 7.06 (2×d, J=8.2 Hz, 1H), 7.13 (d, J=8.2 Hz, 1H), 7.41 (t, J=8.2 Hz, 1H), 7.54 (d, J=1.8 Hz, 1H), 10.71, 10.82 (2×s, 1H).

Workup

  1. washwashed with 2N hydrochloric acid, saturated sodium bicarbonate solution
  2. dry with materiala saturated sodium chloride solution and dried over magnesium sulfate
  3. customThe crude product obtained
  4. concentrationafter concentration
  5. customwas purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 12 g; 0% to 10% methanol/dichloromethane)

Sources & evidence

ORD record
ord-383c9b006f234b6e816092bfdacb81a5
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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