Diisopropylethylamine → 1-Benzyl-4-(1h-indazol-5-yl)-n-[(2s)-tetrahydrofuran-2-ylmethyl]-1h-1,2,3-triazole-5-carboxamide

HRID 240777

反応式

HRID 240777 の反応式
[CH2:1]([N:8]1[C:12]([C:13](O)=[O:14])=[C:11]([C:16]2[CH:17]=[C:18]3[C:22](=[CH:23][CH:24]=2)[NH:21][N:20]=[CH:19]3)[N:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:25]([NH2:31])[C@H:26]1[O:30][CH2:29][CH2:28][CH2:27]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C)C=O>[CH2:1]([N:8]1[C:12]([C:13]([NH:31][CH2:25][C@@H:26]2[CH2:27][CH2:28][CH2:29][O:30]2)=[O:14])=[C:11]([C:16]2[CH:17]=[C:18]3[C:22](=[CH:23][CH:24]=2)[NH:21][N:20]=[CH:19]3)[N:10]=[N:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 641530(S)-(+)-TetrahydrofurfurylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 687368761-Benzyl-4-(1h-indazol-5-yl)-1h-1,2,3-triazole-5-carboxylic acid

生成物 1

HCID 687227371-Benzyl-4-(1h-indazol-5-yl)-n-[(2s)-tetrahydrofuran-2-ylmethyl]-1h-1,2,3-triazole-5-carboxamide

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒4 回

反応条件

温度
50 °C

実験手順

Into a 20 mL vial, a solution of Example 149C (51 mg, 0.16 mmol) dissolved in dimethylformamide (0.5 mL) was added, followed by the addition of (S)-(+)-tetrahydrofurfurylamine (18.2 mg, 0.18 mmol) dissolved in dimethylformamide (0.9 mL). A solution of HATU (68 mg, 0.18 mmol) dissolved in dimethylformamide (0.5 mL) was added followed by a solution of diisopropylethylamine (0.087 mL, 0.5 mmol) dissolved in dimethylformamide (0.5 mL). The mixture was shaken at 50° C. overnight. The reaction was filtered through a Si-Carbonate cartridge (6 mL-1 g) supplied by Silicycle Chemical Division, and the filtrate was transferred to 20 mL vials. The reaction was checked by LC/MS and concentrated to dryness. The residue was dissolved in 1:1 DMSO/methanol and purified by reverse phase HPLC (Agilent, 5%-100% TFA/water gradient, 8 minute run). 1H NMR (300 MHz, DMSO-d6/D2O) δ ppm 1.35-1.54 (m, 1H) 1.64-1.96 (m, 3H) 3.17-3.26 (m, 1H) 3.32-3.38 (m, 1H) 3.50-3.77 (m, 2H) 3.81-4.00 (m, 1H) 5.58-5.74 (m, 2H) 7.21-7.41 (m, 5H) 7.54-7.66 (m, 1H) 7.68-7.84 (m, 1H) 8.01-8.19 (m, 2H). MS (ESI−) m/z 401 (M−H)−.

後処理

  1. additionwas added
  2. additionwas added
  3. filtrationThe reaction was filtered through a Si-Carbonate cartridge (6 mL-1 g)
  4. concentrationconcentrated to dryness
  5. dissolutionThe residue was dissolved in 1:1 DMSO/methanol
  6. custompurified by reverse phase HPLC (Agilent, 5%-100% TFA/water gradient, 8 minute run)

出典と根拠

ORDレコード
ord-f9b02df31d17415b8148fca3706be3c9
出典データセット
uspto-grants-2014_02
特許番号
US08648069B2

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