Diisopropylethylamine → tert-butyl 2-{(3E)-4-[3-methyl-4-({5-(propan-2-yl)-3-[(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosy)oxy]-1H-pyrazol-4-yl}methyl)phenyl]but-3-en-1-yl}-2,9-diazaspiro[5.5]undecane-9-carboxylate

HRID 1625940Notes

Reaction equation

HRID 1625940 reaction equation
CS(O[CH2:6][CH2:7]/[CH:8]=[CH:9]/[C:10]1[CH:15]=[CH:14][C:13]([CH2:16][C:17]2[C:18]([O:25][C@@H:26]3[O:43][C@H:42]([CH2:44][O:45][C:46](=[O:48])[CH3:47])[C@@H:37]([O:38][C:39](=[O:41])[CH3:40])[C@H:32]([O:33][C:34](=[O:36])[CH3:35])[C@H:27]3[O:28][C:29](=[O:31])[CH3:30])=[N:19][NH:20][C:21]=2[CH:22]([CH3:24])[CH3:23])=[C:12]([CH3:49])[CH:11]=1)(=O)=O.Cl.[CH2:51]1[C:56]2([CH2:61][CH2:60][N:59]([C:62]([O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[O:63])[CH2:58][CH2:57]2)[CH2:55][CH2:54][CH2:53][NH:52]1.C(N(C(C)C)CC)(C)C>C(#N)C>[CH3:49][C:12]1[CH:11]=[C:10](/[CH:9]=[CH:8]/[CH2:7][CH2:6][N:52]2[CH2:53][CH2:54][CH2:55][C:56]3([CH2:57][CH2:58][N:59]([C:62]([O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[O:63])[CH2:60][CH2:61]3)[CH2:51]2)[CH:15]=[CH:14][C:13]=1[CH2:16][C:17]1[C:18]([O:25][C@@H:26]2[O:43][C@H:42]([CH2:44][O:45][C:46](=[O:48])[CH3:47])[C@@H:37]([O:38][C:39](=[O:41])[CH3:40])[C@H:32]([O:33][C:34](=[O:36])[CH3:35])[C@H:27]2[O:28][C:29](=[O:31])[CH3:30])=[N:19][NH:20][C:21]=1[CH:22]([CH3:24])[CH3:23]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 71464197Tert-butyl 2,9-diazaspiro[5.5]undecane-9-carboxylate hydrochlorideHCID 86701862(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 methanesulfonate

Product 1

HCID 86715154tert-butyl 2-{(3E)-4-[3-methyl-4-({5-(propan-2-yl)-3-[(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosy)oxy]-1H-pyrazol-4-yl}methyl)phenyl]but-3-en-1-yl}-2,9-diazaspiro[5.5]undecane-9-carboxylateYield 51.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Heat a mixture of (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 methanesulfonate (1.0 g, 1.41 mmol), tert-butyl 2,9-diazaspiro[5.5]undecane-9-carboxylate hydrochloride (451 mg, 1.55 mmol), and diisopropylethylamine (730 mg, 5.64 mmol) in acetonitrile (4 mL) at 80° C. overnight. Remove the solvent under the reduced pressure. Purify the resulting residue by flash chromatography (silica gel, gradient ethyl acetate/dichloromethane from 25-85% over 15 min, then with methanol/dichloromethane from 1-3% over 10 min, 40 g column) to provide the title compound (630 mg, 0.73 mmol). MS (m/z): 867.2, 868.4 (M+1), 865.2, 866.4 (M−1).

Workup

  1. temperatureHeat
  2. customRemove the solvent under the reduced pressure
  3. customPurify the resulting residue by flash chromatography (silica gel, gradient ethyl acetate/dichloromethane from 25-85% over 15 min

Sources & evidence

ORD record
ord-a6c4e39dd639453ea3b1f110dbb42db0
Source dataset
uspto-grants-2014_07
Patent number
US08785404B2

Reaction notes

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