2-Methylpropyl isocyanate → 1-(2-{2-[(3E)-4-(4-{[3-(beta-D-glucopyranosyloxy)-5-(propan-2-yl)-1H-pyrazol-4-yl]methyl}-3-methylphenyl)but-3-en-1-yl]-2,9-diazaspiro[5.5]undec-9-yl}-2-oxoethyl)-3-(2-methylpropyl)urea

HRID 1625944ノート

反応式

HRID 1625944 の反応式
[CH2:1]([N:5]=[C:6]=[O:7])[CH:2]([CH3:4])[CH3:3].Cl.Cl.C([O:13][C@@H:14]1[C@@H:55]([O:56]C(=O)C)[C@H:54]([O:60]C(=O)C)[C@@H:53]([CH2:64][O:65]C(=O)C)[O:52][C@H:15]1[O:16][C:17]1[C:21]([CH2:22][C:23]2[CH:28]=[CH:27][C:26](/[CH:29]=[CH:30]/[CH2:31][CH2:32][N:33]3[CH2:38][CH2:37][CH2:36][C:35]4([CH2:43][CH2:42][N:41]([C:44](=[O:47])[CH2:45][NH2:46])[CH2:40][CH2:39]4)[CH2:34]3)=[CH:25][C:24]=2[CH3:48])=[C:20]([CH:49]([CH3:51])[CH3:50])[NH:19][N:18]=1)(=O)C.C(N(C(C)C)CC)(C)C>ClCCl>[C@@H:15]1([O:16][C:17]2[C:21]([CH2:22][C:23]3[CH:28]=[CH:27][C:26](/[CH:29]=[CH:30]/[CH2:31][CH2:32][N:33]4[CH2:38][CH2:37][CH2:36][C:35]5([CH2:43][CH2:42][N:41]([C:44](=[O:47])[CH2:45][NH:46][C:6]([NH:5][CH2:1][CH:2]([CH3:4])[CH3:3])=[O:7])[CH2:40][CH2:39]5)[CH2:34]4)=[CH:25][C:24]=3[CH3:48])=[C:20]([CH:49]([CH3:51])[CH3:50])[NH:19][N:18]=2)[O:52][C@H:53]([CH2:64][OH:65])[C@@H:54]([OH:60])[C@H:55]([OH:56])[C@H:14]1[OH:13]

参加物

5

反応物 3

HCID 612812-Methylpropyl isocyanateHCID 81531DiisopropylethylamineHCID 867625414-(4-{(1E)-4-[9-(aminoacetyl)-2,9-diazaspiro[5.5]undec-2-yl]but-1-en-1-yl]-2-methylbenzyl}-5-(propan-2-yl)-1H-pyrazol-3-yl 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranoside dihydrochloride

生成物 1

HCID 734385681-(2-{2-[(3E)-4-(4-{[3-(beta-D-glucopyranosyloxy)-5-(propan-2-yl)-1H-pyrazol-4-yl]methyl}-3-methylphenyl)but-3-en-1-yl]-2,9-diazaspiro[5.5]undec-9-yl}-2-oxoethyl)-3-(2-methylpropyl)urea収率 46.2%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

Add isobutyl isocyanate (77 mg, 0.78 mmol) to a solution of 4-(4-{(1E)-4-[9-(aminoacetyl)-2,9-diazaspiro[5.5]undec-2-yl]but-1-en-1-yl]-2-methylbenzyl}-5-(propan-2-yl)-1H-pyrazol-3-yl 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranoside dihydrochloride (350 mg, 0.39 mmol) and diisopropylethylamine (302 mg, 2.34 mmol) in dichloromethane (1.0 mL). After 30 min at room temperature, concentrate to dryness under the reduced pressure. Treat the residue with 2.0 M NH3/methanol (1.0 mL) for 3 hours at room temperature, remove the solvent under the reduced pressure. Purify the resulting residue by preparative HPLC method: high pH, 29% B for 4 min, 29-44% 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—acetonitrile to yield the title compound as solid (134 mg, 0.18 mmol). MS (m/z): 755.2 (M+1), 753.2 (M−1).

後処理

  1. concentrationconcentrate to dryness under the reduced pressure
  2. additionTreat the residue with 2.0 M NH3/methanol (1.0 mL) for 3 hours at room temperature
  3. customremove the solvent under the reduced pressure
  4. customPurify the resulting residue by preparative HPLC method
  5. waithigh pH, 29% B for 4 min
  6. wait29-44% B for 5 min @ 85 mL/min using

出典と根拠

ORDレコード
ord-127fbe4d2b834204b242e21ec46d1df9
出典データセット
uspto-grants-2014_07
特許番号
US08785404B2

反応ノート

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