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

HRID 1096905Notes

Reaction equation

HRID 1096905 reaction equation
[CH:1]1([N:4]2[C:12]3[C:7](=[C:8]([C:16]4[NH:20][N:19]=[N:18][N:17]=4)[CH:9]=[C:10]([C:13]([OH:15])=O)[CH:11]=3)[CH:6]=[CH:5]2)[CH2:3][CH2:2]1.[CH3:21][N:22]1[C:26]([NH:27][C:28]2[CH:29]=[C:30]3[C:40](=[CH:41][CH:42]=2)[O:39][C:33]2([CH2:38][CH2:37][NH:36][CH2:35][CH2:34]2)[CH2:32][CH2:31]3)=[CH:25][CH:24]=[N:23]1.Cl.CCN=C=NCCCN(C)C.Cl.C1C=CC2N([OH:65])N=NC=2C=1>O.CN(C=O)C.C(N(CC)CC)C>[CH:1]1([N:4]2[C:12]3[C:7](=[C:8]([C:16]4[NH:20][N:19]=[N:18][N:17]=4)[CH:9]=[C:10]([C:13]([N:36]4[CH2:35][CH2:34][C:33]5([CH2:32][C:31](=[O:65])[C:30]6[C:40](=[CH:41][CH:42]=[C:28]([NH:27][C:26]7[N:22]([CH3:21])[N:23]=[CH:24][CH:25]=7)[CH:29]=6)[O:39]5)[CH2:38][CH2:37]4)=[O:15])[CH:11]=3)[CH:6]=[CH:5]2)[CH2:3][CH2:2]1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 866355066-[(1-methyl-1H-pyrazol-5-yl)amino]spiro[chroman-2,4'-piperidin)HCID 178524187HCID 178524187, compound

Product 1

HCID 1784818111'-{[1-Cyclopropyl-4-(tetrazol-5-yl)-1H-indol-6-yl]carbonyl}-6-[(1-methyl-1H-pyrazol-5-yl)amino]spiro[chroman-2,4'-piperidin]-4-one

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
90 °C

Procedure

Triethylamine and water (1.5 mL) were added to a DMF (6 mL) solution of 1-cyclopropyl-4-(tetrazol-5-yl)-1H-indole-6-carboxylic acid (348 mg), 6-[(1-methyl-1H-pyrazol-5-yl)amino]spiro[chroman-2,4′-piperidin)]one hydrochloride, WSC hydrochloride and HOBT, and stirred at 90° C. for 30 minutes. Water was added to it at room temperature to obtain a white precipitate. This was dried under reduced pressure, washed with a mixed solvent of methanol and diethyl ether, and again dried under reduced pressure to obtain the title compound as a colorless solid. 1H-NMR (400 MHz, DMSO-d6) δ: 7.92 (1H, s), 7.83 (2H, d, J=3.2 Hz), 7.64 (1H, d, J=3.2 Hz), 7.32 (1H, d, J=1.7 Hz), 7.17-7.12 (3H, m), 7.00 (1H, d, J=9.0 Hz), 5.90 (1H, d, J=1.7 Hz), 4.45-4.05 (1H, br m), 3.60 (3H, s), 3.60-3.53 (1H, m), 3.47-3.21 (3H, br m), 2.83 (2H, s), 2.14-1.70 (4H, br m), 1.14-0.98 (4H, m). MS [M+H]+=564.

Workup

  1. customto obtain a white precipitate
  2. customThis was dried under reduced pressure
  3. washwashed with a mixed solvent of methanol and diethyl ether
  4. customagain dried under reduced pressure

Sources & evidence

ORD record
ord-8e6df10cf0c347e1bd3033a5895c8e81
Source dataset
uspto-grants-2012_03
Patent number
US08138197B2

Reaction notes

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