Hydrochloric Acid → 1'-{[1-Cyclopropyl-4-(tetrazol-5-yl)-1H-indol-6-yl]carbonyl}-6-(6-oxo-1,6-dihydropyridin-3-yl)spiro[chroman-2,4'-piperidin]-4-one

HRID 1096908Notes

Reaction equation

HRID 1096908 reaction equation
Cl.[O:2]=[C:3]1[NH:8][CH:7]=[C:6]([C:9]2[CH:10]=[C:11]3[C:21](=[CH:22][CH:23]=2)[O:20][C:14]2([CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)[CH2:13][C:12]3=[O:24])[CH:5]=[CH:4]1.[CH:25]1([N:28]2[C:36]3[C:31](=[C:32]([C:40]4[NH:44][N:43]=[N:42][N:41]=4)[CH:33]=[C:34]([C:37](O)=[O:38])[CH:35]=3)[CH:30]=[CH:29]2)[CH2:27][CH2:26]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.Cl>CN(C=O)C.O.C(N(CC)CC)C>[CH:25]1([N:28]2[C:36]3[C:31](=[C:32]([C:40]4[NH:44][N:43]=[N:42][N:41]=4)[CH:33]=[C:34]([C:37]([N:17]4[CH2:18][CH2:19][C:14]5([CH2:13][C:12](=[O:24])[C:11]6[C:21](=[CH:22][CH:23]=[C:9]([C:6]7[CH:5]=[CH:4][C:3](=[O:2])[NH:8][CH:7]=7)[CH:10]=6)[O:20]5)[CH2:15][CH2:16]4)=[O:38])[CH:35]=3)[CH:30]=[CH:29]2)[CH2:26][CH2:27]1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 667818066-(6-Oxo-1,6-dihydropyridin-3-yl)spiro[chroman-2,4'-piperidin]-4-one hydrochlorideHCID 178524187HCID 178524187, compound

Product 1

HCID 1785153821'-{[1-Cyclopropyl-4-(tetrazol-5-yl)-1H-indol-6-yl]carbonyl}-6-(6-oxo-1,6-dihydropyridin-3-yl)spiro[chroman-2,4'-piperidin]-4-one

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
50 °C

Procedure

6-(6-Oxo-1,6-dihydropyridin-3-yl)spiro[chroman-2,4′-piperidin]-4-one hydrochloride (208 mg), 1-cyclopropyl-4-(tetrazol-5-yl)-1H-indole-6-carboxylic acid (135 mg), EDCI (115 mg), HOBT (91.2 mg) and triethylamine (0.209 ml) were suspended in DMF (3 ml), and stirred at 50° C. for 16 hours. 1N hydrochloric acid and water were added to the reaction liquid, the formed solid was taken out through filtration, and the resulting solid was recrystallized from methanol to obtain the title compound. 1H-NMR (400 MHz, DMSO-d6) δ: 11.78 (1.0H, s), 7.85-7.82 (2.0H, m), 7.81-7.75 (3.0H, m), 7.67 (1.0H, d, J=2.4 Hz), 7.64 (1.0H, d, J=3.2 Hz), 7.17-7.11 (2.0H, m), 6.40 (1.0H, d, J=9.5 Hz), 4.46-4.12 (1.0H, m), 3.93-3.13 (4.0H, m), 2.92 (2.0H, s), 2.15-1.90 (2.0H, m), 1.88-1.75 (2.0H, m), 1.16-1.08 (2.0H, m), 1.04-0.98 (2.0H, m). MS [M+H]+=562.

Workup

  1. filtrationthe formed solid was taken out through filtration
  2. customthe resulting solid was recrystallized from methanol

Sources & evidence

ORD record
ord-3b2feaf194364e0aa20fcd540bb6e276
Source dataset
uspto-grants-2012_03
Patent number
US08138197B2

Reaction notes

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