1,4-Dioxane hydrochloride → 4-{4-[(1E)-4-(2,6-diazaspiro[3.5]non-2-yl)but-1-en-1-yl]-2-methylbenzyl}-5-(propan-2-yl)-1H-pyrazol-3-yl beta-D-glucopyranoside

HRID 2366519Notes

Reaction equation

HRID 2366519 reaction equation
Cl.O1CCOCC1.[CH3:8][C:9]1[CH:10]=[C:11](/[CH:48]=[CH:49]/[CH2:50][CH2:51][N:52]2[CH2:55][C:54]3([CH2:60][CH2:59][CH2:58][N:57](C(OC(C)(C)C)=O)[CH2:56]3)[CH2:53]2)[CH:12]=[CH:13][C:14]=1[CH2:15][C:16]1[C:17]([O:24][C@@H:25]2[O:42][C@H:41]([CH2:43][O:44]C(=O)C)[C@@H:36]([O:37]C(=O)C)[C@H:31]([O:32]C(=O)C)[C@H:26]2[O:27]C(=O)C)=[N:18][NH:19][C:20]=1[CH:21]([CH3:23])[CH3:22]>ClCCl>[O:24]([C:17]1[C:16]([CH2:15][C:14]2[CH:13]=[CH:12][C:11](/[CH:48]=[CH:49]/[CH2:50][CH2:51][N:52]3[CH2:53][C:54]4([CH2:60][CH2:59][CH2:58][NH:57][CH2:56]4)[CH2:55]3)=[CH:10][C:9]=2[CH3:8])=[C:20]([CH:21]([CH3:23])[CH3:22])[NH:19][N:18]=1)[C@@H:25]1[O:42][C@H:41]([CH2:43][OH:44])[C@@H:36]([OH:37])[C@H:31]([OH:32])[C@H:26]1[OH:27]

Participants

4

Reactant 2

HCID 204431481,4-Dioxane hydrochlorideHCID 86701861tert-butyl 2-{(3E)-4-[3-methyl-4-({5-(propan-2-yl)-3-[(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)oxy]-1 h-pyrazol-4-yl}methyl)phenyl]but-3-en-1-yl}-2,6-diazaspiro[3.5]nonane-6-carboxylate

Product 1

HCID 867018634-{4-[(1E)-4-(2,6-diazaspiro[3.5]non-2-yl)but-1-en-1-yl]-2-methylbenzyl}-5-(propan-2-yl)-1H-pyrazol-3-yl beta-D-glucopyranoside

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Add 4.0 M HCl/1,4-dioxane (1.5 mL, 1.5 mmol) to a solution of tert-butyl 2-{(3E)-4-[3-methyl-4-({5-(propan-2-yl)-3-[(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)oxy]-1 h-pyrazol-4-yl}methyl)phenyl]but-3-en-1-yl}-2,6-diazaspiro[3.5]nonane-6-carboxylate in dichloromethane (2 mL) and stir at rt for 4.0 h. Concentrate the mixture under the reduced pressure to a foamy solid. Treat the solid with 2.0 M ammonia in MeOH (2 mL) overnight. After 18 hours at room temperature, concentrate to remove the solvent under reduced pressure. The resulting residue is purified by preparative HPLC method: high pH, 19% B for 3 min, 19-34 B % for 5 min @ 85 mL/min using a 30×75 mm, 5 um C18XBridge ODB column, solvent A—H2O w NH4HCO3 @ pH 10, solvent B-MeCN to yield the title compound as solid (47 mg, 0.08 mmol). MS (m/z): 570.8, 571.8 (M+1), 568.7, 569.8 (M−1).

Workup

  1. concentrationConcentrate the mixture under the reduced pressure to a foamy solid
  2. additionTreat the solid with 2.0 M ammonia in MeOH (2 mL) overnight
  3. waitAfter 18 hours at room temperature
  4. concentrationconcentrate
  5. customto remove the solvent under reduced pressure
  6. customThe resulting residue is purified by preparative HPLC method
  7. waithigh pH, 19% B for 3 min
  8. wait19-34 B % for 5 min @ 85 mL/min using

Sources & evidence

ORD record
ord-44744f7995794e9bb492a1564dc4d3a1
Source dataset
uspto-grants-2014_04
Patent number
US08697849B2

Reaction notes

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