1-Hydroxybenzotriazole → [5-(1'-{[3,5-Diethoxy-4-(1-methyl-1H-pyrazol-4-yl)phenyl]carbonyl}-4-oxospiro[chroman-2,4'-piperidin]-6-yl)-2H-tetrazol-2-yl]methyl 2,2-dimethylpropanoate

HRID 1096900Notes

Reaction equation

HRID 1096900 reaction equation
C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[CH2:23]([O:25][C:26]1[CH:27]=[C:28]([CH:32]=[C:33]([O:41][CH2:42][CH3:43])[C:34]=1[C:35]1[CH:36]=[N:37][N:38]([CH3:40])[CH:39]=1)[C:29]([OH:31])=O)[CH3:24].Cl.[CH3:45][C:46]([CH3:73])([CH3:72])[C:47]([O:49][CH2:50][N:51]1[N:55]=[N:54][C:53]([C:56]2[CH:57]=[C:58]3[C:68](=[CH:69][CH:70]=2)[O:67][C:61]2([CH2:66][CH2:65][NH:64][CH2:63][CH2:62]2)[CH2:60][C:59]3=[O:71])=[N:52]1)=[O:48]>O.CN(C=O)C.CCN(CC)CC>[CH3:45][C:46]([CH3:73])([CH3:72])[C:47]([O:49][CH2:50][N:51]1[N:55]=[N:54][C:53]([C:56]2[CH:57]=[C:58]3[C:68](=[CH:69][CH:70]=2)[O:67][C:61]2([CH2:62][CH2:63][N:64]([C:29]([C:28]4[CH:32]=[C:33]([O:41][CH2:42][CH3:43])[C:34]([C:35]5[CH:36]=[N:37][N:38]([CH3:40])[CH:39]=5)=[C:26]([O:25][CH2:23][CH3:24])[CH:27]=4)=[O:31])[CH2:65][CH2:66]2)[CH2:60][C:59]3=[O:71])=[N:52]1)=[O:48]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 579310273,5-diethoxy-4-(1-methyl-1H-pyrazol-4-yl)benzoic acidHCID 66781586[5-(4-Oxospiro[chroman-2,4'-piperidin]-6-yl)-tetrazol-2-yl]methyl 2,2-dimethylpropanoate hydrochloride

Product 1

HCID 57930917[5-(1'-{[3,5-Diethoxy-4-(1-methyl-1H-pyrazol-4-yl)phenyl]carbonyl}-4-oxospiro[chroman-2,4'-piperidin]-6-yl)-2H-tetrazol-2-yl]methyl 2,2-dimethylpropanoate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

Et3N (223 μL), HOBT (123 mg) and WSC hydrochloride (154 mg) were added to a DMF (8 mL) solution of 3,5-diethoxy-4-(1-methyl-1H-pyrazol-4-yl)benzoic acid (194 mg) and [5-(4-oxospiro[chroman-2,4′-piperidin]-6-yl)-2H-tetrazol-2-yl]methyl 2,2-dimethylpropanoate hydrochloride (349 mg), and stirred overnight at room temperature. The reaction liquid was poured into saturated saline water, extracted with ethyl acetate, and the organic layer was washed with water and saturated saline water. The organic layer was dried with sodium sulfate, filtered, concentrated, and purified through silica gel column chromatography (hexane/EtOAc) to obtain the title compound. 1H-NMR (400 MHz, CDCl3) δ: 8.69 (1H, d, J=4.0 Hz), 8.32 (1H, dd, J=8.0, 4.0 Hz), 8.14 (1H, s), 7.97 (1H, s), 7.17 (1H, d, J=8.0 Hz), 6.64 (2H, s), 6.50 (2H, s), 4.32-4.18 (1H, m), 4.08 (4H, q, J=8.0 Hz), 3.94 (3H, s), 3.64-3.20 (3H, m), 2.97 (2H, s), 2.10-1.75 (4H, m), 1.37 (6H, t, J=8.0 Hz), 1.22 (9H, s). MS [M+H]+=672.

Workup

  1. customThe reaction liquid
  2. extractionextracted with ethyl acetate
  3. washthe organic layer was washed with water and saturated saline water
  4. dry with materialThe organic layer was dried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified through silica gel column chromatography (hexane/EtOAc)

Sources & evidence

ORD record
ord-c850474617cd41c8aebe2dc54e492ed6
Source dataset
uspto-grants-2012_03
Patent number
US08138197B2

Reaction notes

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