1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 57920186, compound

HRID 18986Notes

Reaction equation

HRID 18986 reaction equation
[Cl:1][C:2]1[C:25]([O:26][CH3:27])=[CH:24][CH:23]=[CH:22][C:3]=1[O:4][C:5]1[CH2:9][N:8]([CH:10]([CH2:14][CH:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[C:11](O)=[O:12])[C:7](=[O:21])[CH:6]=1.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[NH2:49][C:50]1[CH:54]=[CH:53][N:52]([CH2:55][C:56]([CH3:59])([OH:58])[CH3:57])[N:51]=1>ClCCl>[Cl:1][C:2]1[C:25]([O:26][CH3:27])=[CH:24][CH:23]=[CH:22][C:3]=1[O:4][C:5]1[CH2:9][N:8]([CH:10]([CH2:14][CH:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[C:11]([NH:49][C:50]2[CH:54]=[CH:53][N:52]([CH2:55][C:56]([OH:58])([CH3:57])[CH3:59])[N:51]=2)=[O:12])[C:7](=[O:21])[CH:6]=1

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 593449381-(3-amino-1H-pyrazol-1-yl)-2-methylpropan-2-olHCID 668951322-[4-(2-Chloro-3-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-3-(tetrahydro-pyran-4-yl)-propionic acid

Product 1

HCID 57920186HCID 57920186, compoundYield 62%

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]-3-(tetrahydro-pyran-4-yl)-propionic acid (200 mg, 0.51 mmol) in dichloromethane (10 mL) was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (86 mg, 0.56 mmol) and 1-hydroxybenzotriazole (72 mg, 0.53 mmol). The reaction mixture was stirred at 25° C. for 2 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, 94 mg, 0.61 mmol). The reaction mixture was stirred for 18 h at 25° C., under nitrogen. The reaction mixture was diluted with dichloromethane, washed with 2N aqueous hydrochloric acid, saturated sodium bicarbonate solution, a saturated sodium chloride solution and dried over magnesium sulfate. The organic layer was concentrated, and the crude product 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]-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-3-(tetrahydro-pyran-4-yl)-propionamide (166 mg, 62%), as an off-white solid: LR-ES-MS m/z calculated for C26H33ClN4O6 [M]+ 532, observed [M+H]+ 533; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.04 (s, 3H), 1.06 (s, 3H), 1.13-1.30 (m, 2H), 1.37 (br. s., 1H), 1.55-1.73 (m, 3H), 1.72-1.87 (m, 1H), 3.13-3.31 (m, 2H), 3.74-3.87 (m, 2H), 3.89 (br. s., 2H), 3.90 (s, 3H), 4.24 (d, J=18.6 Hz, 1H), 4.60 (d, J=18.6 Hz, 1H), 4.68 (s, 1H), 4.82 (s, 1H), 4.92 (dd, J=10.7, 4.7 Hz, 1H), 6.44 (d, J=2.1 Hz, 1H), 7.09 (d, J=8.5 Hz, 1H), 7.13 (d, J=8.5 Hz, 1H), 7.42 (t, J=8.5 Hz, 1H), 7.54 (d, J=2.1 Hz, 1H), 10.81 (s, 1H).

Workup

  1. stirringThe reaction mixture was stirred for 18 h at 25° C., under nitrogen
  2. washwashed with 2N aqueous hydrochloric acid, saturated sodium bicarbonate solution
  3. dry with materiala saturated sodium chloride solution and dried over magnesium sulfate
  4. concentrationThe organic layer was concentrated
  5. customthe crude product was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 12 g; 0% to 10% methanol/dichloromethane)

Sources & evidence

ORD record
ord-f3da2692f81046e881bf8ae2ed53a7a8
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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