1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 57920140, compound

HRID 19183Notes

Reaction equation

HRID 19183 reaction equation
[OH:1][C@@H:2]([CH2:32]O)[CH2:3][N:4]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:31])[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][CH3:29])[CH:23]=3)=[CH:18][C:17]2=[O:30])[CH2:12][CH:13]([CH3:15])[CH3:14])=[N:5]1.[CH3:34]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])([CH3:32])[CH2:3][N:4]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:31])[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][CH3:29])[CH:23]=3)=[CH:18][C:17]2=[O:30])[CH2:12][CH:13]([CH3:14])[CH3:15])=[N:5]1

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 57920121HCID 57920121, compoundHCID 66899094HMS5552 HCl

Product 1

HCID 57920140HCID 57920140, compoundYield 79.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

A solution of (S)-2-[4-(3-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid (prepared as in Example 160, 300 mg, 0.94 mmol) in dichloromethane (20 mL) was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (161 mg, 1.03 mmol) and 1-hydroxybenzotriazole (135 mg, 0.99 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, 175 mg, 1.13 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; 0% to 10% methanol/dichloromethane) to afford (S)-2-[4-(3-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-amide (340 mg, 79%) as a light brown powder: HR-ES-MS m/z calculated for C24H32N4O5 [M+H]+ 456, observed 457; 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), 1.39-1.64 (m, 2H), 1.67-1.82 (m, 1H), 3.77 (s, 3H), 3.89 (s, 2H), 4.16 (d, J=18.4 Hz, 1H), 4.57 (d, J=18.4 Hz, 1H), 4.68 (s, 1H), 4.84-4.93 (m 1H), 4.87 (s, 1H), 6.44 (d, J=2.1 Hz, 1H), 6.83-6.91 (m, 3H), 7.37 (t, J=8.2 Hz, 1H), 7.53 (d, J=2.1 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; 0% to 10% methanol/dichloromethane)

Sources & evidence

ORD record
ord-2b5b3e155c9e4d4a902a96b7710d2b25
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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