Water → N-(4-fluoro-3-methoxybenzyl)-6-((R)-5-((2R,5R)-5-(hydroxymethyl)-1,4-dioxan-2-yl)-4,5-dihydroisoxazol-3-yl)-2-methylpyrimidine-4-carboxamide

HRID 572655

反応式

HRID 572655 の反応式
CC1C=CC(S([O:11][CH2:12][C@@H:13]2[CH2:18][O:17][C@@H:16]([C@@H:19]3[O:23][N:22]=[C:21]([C:24]4[CH:29]=[C:28]([C:30](=[O:42])[NH:31][CH2:32][C:33]5[CH:38]=[CH:37][C:36]([F:39])=[C:35]([O:40][CH3:41])[CH:34]=5)[N:27]=[C:26]([CH3:43])[N:25]=4)[CH2:20]3)[CH2:15][O:14]2)(=O)=O)=CC=1.O.[OH-].[Na+]>C([O-])(=O)C.C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C.CCOC(C)=O>[F:39][C:36]1[CH:37]=[CH:38][C:33]([CH2:32][NH:31][C:30]([C:28]2[CH:29]=[C:24]([C:21]3[CH2:20][C@H:19]([C@H:16]4[CH2:15][O:14][C@H:13]([CH2:12][OH:11])[CH2:18][O:17]4)[O:23][N:22]=3)[N:25]=[C:26]([CH3:43])[N:27]=2)=[O:42])=[CH:34][C:35]=1[O:40][CH3:41]

参加物

7

反応物 3

HCID 962WaterHCID 14798Sodium HydroxideHCID 86675913((2S,5R)-5-((R)-3-(6-((4-fluoro-3-methoxybenzyl)carbamoyl)-2-methylpyrimidin-4-yl)-4,5-dihydroisoxazol-5-yl)-1,4-dioxan-2-yl)methyl 4-methylbenzenesulfonate

生成物 1

HCID 86675912N-(4-fluoro-3-methoxybenzyl)-6-((R)-5-((2R,5R)-5-(hydroxymethyl)-1,4-dioxan-2-yl)-4,5-dihydroisoxazol-3-yl)-2-methylpyrimidine-4-carboxamide収率 61.5%

試薬・触媒・溶媒 3

HCID 82707Tetrabutylammonium Acetate触媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A solution of ((2S,5R)-5-((R)-3-(6-((4-fluoro-3-methoxybenzyl)carbamoyl)-2-methylpyrimidin-4-yl)-4,5-dihydroisoxazol-5-yl)-1,4-dioxan-2-yl)methyl 4-methylbenzenesulfonate (0.7 g, 1.13 mmol, Preparation #G.6) and tetra butyl ammonium acetate (0.72 g, 2.34 mmol, Aldrich) in DMF (5 mL) were stirred for 3 h at 70° C. The reaction mixture was cooled to RT, the reaction vessel was charged sequentially with water (10 mL) and 1.0N aqueous sodium hydroxide (5 mL). After string for 20 minu at RT it was diluted with EtOAc (200 mL) and washed with 50% aqueous sodiumchloride solution (2×150 mL). The organic layer was dried over sodiumsulphate and evaporated to dryness. The resulting crude material was purified by column chromatography on silica gel eluting with 60% EtOAc in hexane to afford N-(4-fluoro-3-methoxybenzyl)-6-((R)-5-((2R,5R)-5-(hydroxymethyl)-1,4-dioxan-2-yl)-4,5-dihydroisoxazol-3-yl)-2-methylpyrimidine-4-carboxamide 0.32 g (61%); 1H NMR (400 MHz, DMSO): δ 9.48 (t, J=6.4 Hz, 1H), 8.11 (s, 1H), 7.15-7.09 (m, 2H), 6.86-6.81 (m, 1H), 4.80-4.70 (m, 2H), 4.69 (t, J=5.2 Hz, 1H), 4.46 (d, J=6.4 Hz, 2H), 3.88-3.82 (m, 2H), 3.79 (s, 3H), 3.56-3.34 (m, 6H), 2.75 (s, 3H); LC/MS (Table 1, Method d) Rt=0.74 min; MS m/z: 461.1 (m+H)+.

後処理

  1. washwashed with 50% aqueous sodiumchloride solution (2×150 mL)
  2. dry with materialThe organic layer was dried over sodiumsulphate
  3. customevaporated to dryness
  4. customThe resulting crude material was purified by column chromatography on silica gel eluting with 60% EtOAc in hexane

出典と根拠

ORDレコード
ord-2b6b7f73e7b14c36848b49ad5e58b418
出典データセット
uspto-grants-2015_05
特許番号
US09029409B2

関連ノート

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