1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 16722380, compound

HRID 555269Notes

Reaction equation

HRID 555269 reaction equation
[CH3:1][CH2:2][O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([C:15]([OH:17])=O)=[CH:10][CH:9]=2)=[O:5].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[CH3:40][C:41]12[CH2:48][CH:45]([NH:46][CH2:47]1)[CH2:44][C:43]([CH3:50])([CH3:49])[CH2:42]2.CCN(C(C)C)C(C)C>CN(C=O)C>[CH2:2]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([C:15]([N:46]1[CH2:47][C:41]3([CH3:40])[CH2:48][CH:45]1[CH2:44][C:43]([CH3:50])([CH3:49])[CH2:42]3)=[O:17])=[CH:10][CH:9]=2)=[O:5])[CH3:1]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 180713652-(Ethoxycarbonyl)-1H-indole-5-carboxylic acidHCID 66987540HCID 66987540, compound

Product 1

HCID 16722380HCID 16722380, compoundYield 57.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1H-Indole-2,5-dicarboxylic acid 2-ethyl ester (890 mg, 3.8 mmol) in dry DMF (10 mL) at room temperature under an inert atmosphere of nitrogen was added HOBt (570 mg, 4.2 mmol) and EDAC (951 mg, 4.9 mmol), and the resulting solution was stirred for 30 min. 1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane hydrochloride (796 mg, 4.2 mmol) was added to the solution followed by DIPEA (1.98 mL, 11.4 mmol), and the reaction mixture was stirred for 16 h at room temperature. The reaction was quenched by the addition of water (20 mL) followed by extraction with DCM (3×50 mL). The combined organic phases were dried (MgSO4), filtered, and evaporated in vacuo. The resulting solid was purified by silica gel chromatography using a mixture of ethyl acetate and heptane (1:2) as eluent. Pure fractions were collected, the solvent evaporated in vacuo and dried in vacuo at 50° C. affording 800 mg (57%) of the title compound as a solid. MS-ESI m/z 369; 1H NMR (300 MHz, CDCl3) δ 0.94 (d, 3H), 1.04 (d, 3H), 1.14-1.19 (m, 4H), 1.24-1.29 (m, 2H), 1.39-1.45 (m, 4H), 1.58-1.63 (m, 1H), 1.76-1.79 (m, 1H), 3.25-3.30 (m, 1H), 3.35 (d) and 3.65 (d, 1H), 4.06-4.09 (m) and 4.64-4.67 (m, 1H), 4.42 (q, 2H), 7.27 (s, 1H), 7.39-7.46 (m, 2H), 7.82 (d, 1H), 9.05 (s, 1H).

Workup

  1. stirringthe reaction mixture was stirred for 16 h at room temperature
  2. customThe reaction was quenched by the addition of water (20 mL)
  3. extractionfollowed by extraction with DCM (3×50 mL)
  4. dry with materialThe combined organic phases were dried (MgSO4)
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe resulting solid was purified by silica gel chromatography
  8. additiona mixture of ethyl acetate and heptane (1:2) as eluent
  9. customPure fractions were collected
  10. customthe solvent evaporated in vacuo
  11. customdried in vacuo at 50° C.

Sources & evidence

ORD record
ord-d4d0a4a0619246b89bac53ceb8d4b777
Source dataset
uspto-grants-2011_11
Patent number
US08053431B2

Reaction notes

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