1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-carbamoylmethyl-1'-[(1-cyclopropyl-4-methoxy-1H-indol-6-yl)carbonyl]-4-oxo-spiro[chroman-2,4'-piperidine]-6-carboxamide

HRID 420134Notes

Reaction equation

HRID 420134 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.[C:40]([CH2:43][NH:44][C:45]([C:47]1[CH:48]=[C:49]2[C:59](=[CH:60][CH:61]=1)[O:58][C:52]1([CH2:57][CH2:56][NH:55][CH2:54][CH2:53]1)[CH2:51][C:50]2=[O:62])=[O:46])(=[O:42])[NH2:41]>CN(C=O)C.O.CCN(CC)CC>[C:40]([CH2:43][NH:44][C:45]([C:47]1[CH:48]=[C:49]2[C:59](=[CH:60][CH:61]=1)[O:58][C:52]1([CH2:57][CH2:56][N:55]([C:34]([C:31]3[CH:32]=[C:33]4[C:28]([CH:27]=[CH:26][N:25]4[CH:22]4[CH2:23][CH2:24]4)=[C:29]([O:37][CH3:38])[CH:30]=3)=[O:36])[CH2:54][CH2:53]1)[CH2:51][C:50]2=[O:62])=[O:46])(=[O:42])[NH2:41]

Participants

8

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 666494031-cyclopropyl-4-methoxy-1H-indole-6-carboxylic acidHCID 66649519N-Carbamoylmethyl-4-oxospiro[chroman-2,4'-piperidine]-6-carboxamide hydrochloride

Product 1

HCID 24966803N-carbamoylmethyl-1'-[(1-cyclopropyl-4-methoxy-1H-indol-6-yl)carbonyl]-4-oxo-spiro[chroman-2,4'-piperidine]-6-carboxamide

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 (145 mg) and N-carbamoylmethyl-4-oxo-spiro[chroman-2,4′-piperidine]-6-carboxamide hydrochloride (354 mg) in DMF (3 mL), and the mixture was stirred overnight at 50° C. After cooled to room temperature, the mixture was diluted with water, and the formed solid was collected by filtration. The solid was dried and purified on silica gel preparative TLC (development: CHCl3/MeOH) to obtain the intended compound as colorless foam. 1H-NMR (400 MHz, DMSO-d6) δ: 8.84-8.72 (1H, m), 8.80-8.62 (1H, m), 8.33-8.29 (1H, m), 8.08 (1H, dd, J=8.7, 2.3 Hz), 7.35 (1H, s), 7.28 (1H, d, J=3.2 Hz), 7.23-7.16 (2H, m), 6.99 (1H, s), 6.58 (1H, d, J=1.0 Hz), 6.39 (1H, dd, J=3.2, 0.7 Hz), 4.40-4.02 (2H, br m), 3.87 (3H, s), 3.80-3.76 (2H, br m), 3.48-3.25 (4H, m), 2.98 (2H, s), 2.06-1.56 (2H, m), 1.09-1.01 (2H, m), 0.95-0.89 (2H, m); MS [M+H]+=531.

Workup

  1. temperatureAfter cooled to room temperature
  2. filtrationthe formed solid was collected by filtration
  3. customThe solid was dried
  4. custompurified on silica gel preparative TLC (development: CHCl3/MeOH)

Sources & evidence

ORD record
ord-f40826c187444959b1b3e91431d2be16
Source dataset
uspto-grants-2012_01
Patent number
US08093389B2

Reaction notes

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