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 931682Notes

Reaction equation

HRID 931682 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]-1h-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-918327cdbfc54ad0931e39fc6840587b
Source dataset
uspto-grants-2016_03
Patent number
US09296775B2

Reaction notes

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