1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 6-[(1-methyl-1H-pyrazol-5-yl)amino]-1'-{[2-phenyl-6-(tetrazol-5-yl)pyridin-4-yl]carbonyl}spiro[chroman-2,4'-piperidin]-4-one

HRID 1096884Notes

Reaction equation

HRID 1096884 reaction equation
Cl.[CH3:2][N:3]1[C:7]([NH:8][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:6][CH:5]=[N:4]1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[C:48]1([C:54]2[CH:55]=[C:56]([CH:60]=[C:61]([C:63]3[NH:67][N:66]=[N:65][N:64]=3)[N:62]=2)[C:57](O)=[O:58])[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1>O.CN(C=O)C.C(N(CC)CC)C>[CH3:2][N:3]1[C:7]([NH:8][C:9]2[CH:10]=[C:11]3[C:21](=[CH:22][CH:23]=2)[O:20][C:14]2([CH2:15][CH2:16][N:17]([C:57]([C:56]4[CH:60]=[C:61]([C:63]5[NH:67][N:66]=[N:65][N:64]=5)[N:62]=[C:54]([C:48]5[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=5)[CH:55]=4)=[O:58])[CH2:18][CH2:19]2)[CH2:13][C:12]3=[O:24])=[CH:6][CH:5]=[N:4]1

Participants

8

Reactant 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 666494456-[(1-Methyl-1H-pyrazol-5-yl)amino]spiro[chroman-2,4'-piperidin]-4-one hydrochlorideHCID 1785241162-Phenyl-6-(tetrazol-5-yl)-isonicotinic acid

Product 1

HCID 1784818106-[(1-methyl-1H-pyrazol-5-yl)amino]-1'-{[2-phenyl-6-(tetrazol-5-yl)pyridin-4-yl]carbonyl}spiro[chroman-2,4'-piperidin]-4-one

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
60 °C

Procedure

6-[(1-Methyl-1H-pyrazol-5-ylamino)]spiro[chroman-2,4′-piperidin]-4-one hydrochloride (117 mg), 1-hydroxybenzotriazole monohydrate (53 mg), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (68 mg), triethylamine (94 μL) and water (1 mL) were added in that order to a DMF (3 mL) solution of 2-phenyl-6-(tetrazol-5-yl)-isonicotinic acid (75 mg), and stirred at 60° C. for 1 hour. Water was added to the reaction liquid, and the resulting precipitate was taken out through filtration, washed with hexane/ethyl acetate=2/1, and dried to obtain the title compound as a yellow solid. 1H-NMR (400 MHz, DMSO-d6) δ: 8.37 (2.0H, d, J=6.8 Hz), 8.17 (1.0H, s), 8.08 (1.0H, br s), 7.93 (1.0H, s), 7.61-7.50 (3.0H, m), 7.32 (1.0H, d, J=2.0 Hz), 7.18-7.12 (2.0H, m), 6.99 (1.0H, d, J=8.4 Hz), 5.89 (1.0H, s), 4.31-4.27 (1.0H, m), 3.60 (3.0H, s), 3.50-3.20 (3.0H, m), 2.82 (2.0H, s), 2.12-2.05 (1.0H, m), 1.90-1.78 (3.0H, m). MS [M−H]+=560.

Workup

  1. filtrationthe resulting precipitate was taken out through filtration
  2. washwashed with hexane/ethyl acetate=2/1
  3. customdried

Sources & evidence

ORD record
ord-d689236cf06942adad4783e953726409
Source dataset
uspto-grants-2012_03
Patent number
US08138197B2

Reaction notes

Loading…