1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 57920070, compound

HRID 18993Notes

Reaction equation

HRID 18993 reaction equation
[CH:1]1([CH2:7][C@H:8]([N:12]2[CH2:16][C:15]([O:17][CH2:18][CH:19]3[O:24][C:23]4[CH:25]=[CH:26][CH:27]=[CH:28][C:22]=4[O:21][CH2:20]3)=[CH:14][C:13]2=[O:29])[C:9]([OH:11])=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[NH2:51][C:52]1[CH:56]=[CH:55][N:54]([CH2:57][C:58]([CH3:61])([OH:60])[CH3:59])[N:53]=1>ClCCl>[CH:1]1([CH2:7][C@H:8]([N:12]2[CH2:16][C:15]([O:17][CH2:18][CH:19]3[O:24][C:23]4[CH:25]=[CH:26][CH:27]=[CH:28][C:22]=4[O:21][CH2:20]3)=[CH:14][C:13]2=[O:29])[C:9]([NH:51][C:52]2[CH:56]=[CH:55][N:54]([CH2:57][C:58]([OH:60])([CH3:59])[CH3:61])[N:53]=2)=[O:11])[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 66899975HCID 66899975, compound

Product 1

HCID 57920070HCID 57920070, compoundYield 24%

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-2-ylmethoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-propionic acid (151 mg, 0.55 mmol) in dichloromethane (10 mL) was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (63 mg, 0.39 mmol) and 1-hydroxybenzotriazole (52 mg, 0.38 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, 67 mg, 0.43 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 on Gilson HPLC system (C18 column, 10-99% acetonitrile/water gradient) to afford (S)-3-cyclohexyl-2-[4-(2,3-dihydro-benzo[1,4]dioxin-2-ylmethoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-(2-hydroxy-2-methyl-propyl)-1-H-pyrazol-3-yl]-propionamide (47 mg, 24%) as a white solid: HR-ES-MS m/z calculated for C29H38N4O6 [M+H]+ 539.2864, observed 539.2865; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.81-0.99 (m, 2H) 1.05 (s, 3H) 1.07-1.30 (m, 4H) 1.50-1.83 (m, 7H) 3.89 (s, 2H) 3.98 (dd, J=18.1, 4.0 Hz, 1H) 4.09 (dd, J=11.3, 7.5 Hz, 1H) 4.18-4.34 (m, 2H) 4.34-4.45 (m, 1H) 4.53-4.63 (m, 1H) 4.67 (s, 1H) 4.86 (dd, J=11.3, 4.0 Hz, 1H) 5.25 (s, 1H) 6.42 (d, J=2.1 Hz, 1H) 6.79-6.99 (m, 4H) 7.52 (d, J=2.1 Hz, 1H) 10.70 (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 on Gilson HPLC system (C18 column, 10-99% acetonitrile/water gradient)

Sources & evidence

ORD record
ord-d2f53c3bf7b9408b9aa67d86bd3f1a73
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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