1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 44253628, compound

HRID 18972

Reaction equation

HRID 18972 reaction equation
[CH:1]1([CH2:7][C@H:8]([N:12]2[CH2:16][C:15]([O:17][C:18]3[C:27]4[O:26][CH2:25][CH2:24][O:23][C:22]=4[CH:21]=[CH:20][CH:19]=3)=[CH:14][C:13]2=[O:28])[C:9](O)=[O:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[NH2:50][C:51]1[CH:55]=[CH:54][N:53]([CH2:56][C:57]([CH3:60])([OH:59])[CH3:58])[N:52]=1>ClCCl>[CH:1]1([CH2:7][C@H:8]([N:12]2[CH2:16][C:15]([O:17][C:18]3[C:27]4[O:26][CH2:25][CH2:24][O:23][C:22]=4[CH:21]=[CH:20][CH:19]=3)=[CH:14][C:13]2=[O:28])[C:9]([NH:50][C:51]2[CH:55]=[CH:54][N:53]([CH2:56][C:57]([OH:59])([CH3:58])[CH3:60])[N:52]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]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 66899332(S)-3-cyclohexyl-2-[4-(2,3-dihydro-benzo[1,4]dioxin-5-yloxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-propionic acid

Product 1

HCID 44253628HCID 44253628, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

A solution of (S)-3-cyclohexyl-2-[4-(2,3-dihydro-benzo[1,4]dioxin-5-yloxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-propionic acid (200 mg, 0.52 mmol) in dichloromethane (10 mL) was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (81 mg, 0.52 mmol) and 1-hydroxybenzotriazole (75 mg, 0.54 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, 88 mg, 0.57 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 100% ethyl acetate/hexanes) to afford (S)-3-cyclohexyl-2-[4-(2,3-dihydro-benzo[1,4]dioxin-5-yloxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-propionamide (117 mg, 43%) as a white solid: LR-ES-MS m/z calculated for C28H36N4O6 [M]+ 524, observed [M+H]+ 525; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.74-1.33 (m, 6H) 1.04 (s, 3H) 1.06 (s, 3H) 1.49-1.89 (m, 7H) 3.89 (s, 2H) 4.11 (d, J=18.4 Hz, 1H) 4.28 (s, 4H) 4.52 (d, J=18.4 Hz, 1H) 4.68 (s, 1H) 4.84 (s, 1H) 4.89 (dd, J=10.6, 4.8 Hz, 1H) 6.44 (d, J=2.1 Hz, 1H) 6.72-6.95 (m, 3H) 7.53 (d, J=2.1 Hz, 1H) 10.77 (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 100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-1291d12aef1343faa47e4acfceb9848d
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Linked notes

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