1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 57920103, compound

HRID 19182Notes

Reaction equation

HRID 19182 reaction equation
[OH:1][C@@H:2]([CH2:33]O)[CH2:3][N:4]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:32])[C@@H:11]([N:16]2[CH2:20][C:19]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH2:29][CH3:30])[CH:23]=3)=[CH:18][C:17]2=[O:31])[CH2:12][CH:13]([CH3:15])[CH3:14])=[N:5]1.[CH3:35]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]([CH3:33])([CH3:35])[CH2:3][N:4]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:32])[C@@H:11]([N:16]2[CH2:20][C:19]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH2:29][CH3:30])[CH:23]=3)=[CH:18][C:17]2=[O:31])[CH2:12][CH:13]([CH3:15])[CH3:14])=[N:5]1

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 57920175(S)-2-[4-(3-Ethoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-amideHCID 66899094HMS5552 HCl

Product 1

HCID 57920103HCID 57920103, compoundYield 51.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

A solution of (S)-2-[4-(3-ethoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid (prepared as in Example 162, 300 mg, 0.90 mmol) in dichloromethane (20 mL) was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (154 mg, 0.99 mmol) and 1-hydroxybenzotriazole (128 mg, 0.95 mmol). The reaction mixture was stirred at 25° C. for 1 h followed by the addition of 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032 Example 80, 168 mg, 1.08 mmol). The reaction mixture was stirred for 18 h at 25° C., under nitrogen. The reaction mixture was 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 40 g; (20% to 100% ethyl acetate/hexanes) to afford (S)-2-[4-(3-ethoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-amide (217 mg, 51%) as a yellow powder: HR-ES-MS m/z calculated for C25H34N4O5 [M+H]+ 470, observed 471; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.90 (d, J=6.3 Hz, 3H), 0.93 (d, J=6.3 Hz, 3H), 1.04 (br. s., 3H), 1.06 (br. s., 3H), 1.31 (t, J=6.8 Hz, 3H), 1.38-1.64 (m, 2H), 1.67-1.84 (m, 1H), 3.89 (s, 2H), 4.04 (q, J=6.8 Hz, 2H), 4.16 (d, J=18.1 Hz, 1H), 4.56 (d, J=18.1 Hz, 4.68 (s, 1H), 4.86 (s, 1H), 4.87-4.93 (m, 1H), 6.44 (d, J=1.8 Hz, 1H), 6.78-6.92 (m, 3H), 7.35 (t, J=8.3 Hz, 1H), 7.53 (d, J=1.8 Hz, 1H), 10.79 (s, 1H).

Workup

  1. stirringThe reaction mixture was stirred for 18 h at 25° C., under nitrogen
  2. washwashed with 2N hydrochloric acid, saturated sodium bicarbonate solution
  3. dry with materiala saturated sodium chloride solution and dried over magnesium sulfate
  4. customThe crude product obtained
  5. concentrationafter concentration
  6. customwas purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 40 g

Sources & evidence

ORD record
ord-44610c6b7f7a4145ac91eabee1581cda
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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