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Diisopropylethylamine → 2-((3-(5-Phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)methyl)-2,5,7-triazaspiro[3.4]octane-6,8-dione

HRID 1506353
ノート
印刷プレビュー

反応式

HRID 1506353 の反応式
Br[CH2:2][C:3]1[CH:4]=[C:5]2[C:28](=[CH:29][CH:30]=1)[C:9]1=[N:10][O:11][C:12]([C:13]3[C:17]([C:18]([F:21])([F:20])[F:19])=[C:16]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[O:15][N:14]=3)=[C:8]1[CH2:7][CH2:6]2.[CH2:31]1[C:34]2([C:38](=[O:39])[NH:37][C:36](=[O:40])[NH:35]2)[CH2:33][NH:32]1.C(OC1C=CC(C2ON=C3C4C(CCC=23)=CC(C=C)=CC=4)=C(C(F)(F)F)C=1)(C)C.C(N(CC)C(C)C)(C)C.C(=O)(O)[O-].[Na+]>CN(C)C=O>[C:22]1([C:16]2[O:15][N:14]=[C:13]([C:12]3[O:11][N:10]=[C:9]4[C:28]5[C:5]([CH2:6][CH2:7][C:8]=34)=[CH:4][C:3]([CH2:2][N:32]3[CH2:31][C:34]4([C:38](=[O:39])[NH:37][C:36](=[O:40])[NH:35]4)[CH2:33]3)=[CH:30][CH:29]=5)[C:17]=2[C:18]([F:21])([F:19])[F:20])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 666007202,5,7-Triazaspiro[3.4]octane-6,8-dioneHCID 671678437-(Bromomethyl)-3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazoleHCID 671709643-(4-Isopropoxy-2-(trifluoromethyl)phenyl)-7-vinyl-4,5-dihydronaphtho[1,2-c]isoxazole

生成物 1

HCID 67170833
2-((3-(5-Phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)methyl)-2,5,7-triazaspiro[3.4]octane-6,8-dione
収率 65.4%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

To a stirred mixture of 7-(bromomethyl)-3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazole (Preparation 6C, 25 mg, 0.053 mmol), 2,5,7-triazaspiro[3.4]octane-6,8-dione, hydrochloric acid (Preparation 17B, 11 mg, 0.079 mmol), and anhydrous dimethylformamide (0.5 mL) was added N,N-diisopropylethylamine (0.046 mL, 0.263 mmol) dropwise at 0° C. The mixture was stirred at 0° C. for 30 min and at room temperature for 80 min. The reaction mixture was concentrated and subjected to prep HPLC conditions (PHENOMENEX® Luna Axia 30×100 mm; 10 min. gradient; solvent A=10% MeOH, 90% H2O, 0.1% TFA, solvent B=90% MeOH, 10% H2O, 0.1% TFA). The desired fractions were concentrated to yield an aqueous suspension of the product, to which saturated aqueous sodium bicarbonate solution (1 mL) was added to make the mixture basic. The solid was filtered and washed with water (3×1 mL) and then lyophilized to give 2-((3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)methyl)-2,5,7-triazaspiro[3.4]octane-6,8-dione (19 mg, 0.034 mmol, 65.4% yield) as a white solid. The compound had an HPLC retention time=3.19 min (condition C); LC/MS M+1=536.3; 1H NMR (400 MHz, MeOD) δ ppm 7.92 (1H, d, J=7.9 Hz), 7.77 (2H, d, J=7.3 Hz), 7.58-7.71 (3H, m), 7.40 (1H, s), 7.37 (1H, d, J=7.7 Hz), 3.78 (2H, s), 3.75 (2H, d, J=8.6 Hz), 3.48 (2H, d, J=8.8 Hz), 3.08 (4H, s).

後処理

  1. concentrationThe reaction mixture was concentrated
  2. customHPLC conditions (PHENOMENEX® Luna Axia 30×100 mm; 10 min. gradient; solvent A=10% MeOH, 90% H2O, 0.1% TFA, solvent B=90% MeOH, 10% H2O, 0.1% TFA)
  3. concentrationThe desired fractions were concentrated
  4. customto yield
  5. additionan aqueous suspension of the product
  6. filtrationThe solid was filtered
  7. washwashed with water (3×1 mL)

出典と根拠

ORDレコード
ord-eded28a1ed0b415788846aadb708052c
出典データセット
uspto-grants-2015_12
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09216972B2

反応ノート

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