1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1'-[(1-cyclopropyl-4-methoxy-1H-indol-6-yl)carbonyl]-6-(5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)spiro[chroman-2,4'-piperidin]-4-one

HRID 420133Notes

Reaction equation

HRID 420133 reaction equation
C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[CH:22]1([N:25]2[C:33]3[C:28](=[C:29]([O:37][CH3:38])[CH:30]=[C:31]([C:34]([OH:36])=O)[CH:32]=3)[CH:27]=[CH:26]2)[CH2:24][CH2:23]1.Cl.[O:40]=[C:41]1[NH:45][N:44]=[C:43]([C:46]2[CH:47]=[C:48]3[C:58](=[CH:59][CH:60]=2)[O:57][C:51]2([CH2:56][CH2:55][NH:54][CH2:53][CH2:52]2)[CH2:50][C:49]3=[O:61])[NH:42]1>CN(C=O)C.O.CCN(CC)CC>[CH:22]1([N:25]2[C:33]3[C:28](=[C:29]([O:37][CH3:38])[CH:30]=[C:31]([C:34]([N:54]4[CH2:55][CH2:56][C:51]5([CH2:50][C:49](=[O:61])[C:48]6[C:58](=[CH:59][CH:60]=[C:46]([C:43]7[NH:42][C:41](=[O:40])[NH:45][N:44]=7)[CH:47]=6)[O:57]5)[CH2:52][CH2:53]4)=[O:36])[CH:32]=3)[CH:27]=[CH:26]2)[CH2:23][CH2:24]1

Participants

8

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 666494031-cyclopropyl-4-methoxy-1H-indole-6-carboxylic acidHCID 1363426456-(5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)spiro[chroman-2,4'-piperidin]-4-one hydrochloride

Product 1

HCID 1359290291'-[(1-cyclopropyl-4-methoxy-1H-indol-6-yl)carbonyl]-6-(5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)spiro[chroman-2,4'-piperidin]-4-one

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
50 °C

Procedure

Et3N (209 uL), HOBT (91.2 mg) and WSC (115 mg) were added to a suspension of 1-cyclopropyl-4-(methyloxy)-1H-indole-6-carboxylic acid (116 mg) and 6-(5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)spiro[chroman-2,4′-piperidin]-4-one hydrochloride (202 mg) in DMF (3 mL), and the mixture was stirred overnight at 50° C. Water was added to the reaction mixture, and the formed solid was collected by filtration. The solid was purified by silica gel column chromatography (CHCl3/MeOH) to obtain the intended compound as colorless foam. 1H-NMR (400 MHz, DMSO-d6) δ: 8.06 (1H, d, J=2.3 Hz), 8.00 (1H, dd, J=8.7, 2.3 Hz), 7.29 (1H, d, J=3.2 Hz), 7.26 (1H, d, J=8.7 Hz), 7.24-7.21 (3H, m), 6.58 (1H, d, J=1.0 Hz), 6.40 (1H, dd, J=3.2, 1.0 Hz), 4.44-4.08 (1H, br m), 3.87 (3H, s), 3.80-3.25 (4H, m), 2.97 (2H, s), 2.10-1.70 (4H, m), 1.09-1.01 (2H, m), 0.96-0.89 (2H, m); MS [M+H]+=514.

Workup

  1. filtrationthe formed solid was collected by filtration
  2. customThe solid was purified by silica gel column chromatography (CHCl3/MeOH)

Sources & evidence

ORD record
ord-d03e0895f3464cdaa5fb566883ee7315
Source dataset
uspto-grants-2012_01
Patent number
US08093389B2

Reaction notes

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