Hydrochloric Acid → (R)-1-[4-(2-Methyl-4-phenyl-5,8-dihydro-6H-pyrido[3,4-d]pyrimidin-7-yl)-pyrimidin-2-yl]ethanol

HRID 586172ノート

反応式

HRID 586172 の反応式
C([O:6][C@@H:7]([C:9]1[N:14]=[C:13]([N:15]2[CH2:24][CH2:23][C:22]3[C:21]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)=[N:20][C:19]([CH3:31])=[N:18][C:17]=3[CH2:16]2)[CH:12]=[CH:11][N:10]=1)[CH3:8])(=O)CCC.Cl.[OH-].[Na+]>O1CCOCC1>[CH3:31][C:19]1[N:20]=[C:21]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:22]2[CH2:23][CH2:24][N:15]([C:13]3[CH:12]=[CH:11][N:10]=[C:9]([C@H:7]([OH:6])[CH3:8])[N:14]=3)[CH2:16][C:17]=2[N:18]=1

参加物

5

反応物 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 53875213(R)-1-[4-(2-methyl-4-phenyl-5,8-dihydro-6H-pyrido[3,4-d]pyrimidin-7-yl)-pyrimidin-2-yl]-ethyl butyrate

生成物 1

HCID 20767624(R)-1-[4-(2-Methyl-4-phenyl-5,8-dihydro-6H-pyrido[3,4-d]pyrimidin-7-yl)-pyrimidin-2-yl]ethanol収率 88%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

実験手順

To a solution of (R)-1-[4-(2-methyl-4-phenyl-5,8-dihydro-6H-pyrido[3,4-d]pyrimidin-7-yl)-pyrimidin-2-yl]-ethyl butyrate (prepared according to the method of Example 86, Step E, 11.0 g, 26.4 mmol) in dioxane (13 mL) was added concentrated hydrochloric acid (22 mL, 264 mmol). This mixture was stirred at room temperature overnight, cooled to 0° C., neutralized via slow addition of 6 N aqueous sodium hydroxide, and extracted with ethyl acetate (4×). The combined organic extracts were dried over sodium sulfate, filtered, evaporated, and purified by flash column chromatography (2→5% methanol/ethyl acetate) to give an oil which after titration with hexanes provided 8.0 g (88%) of the title compound as a white solid. mp: 114-116° C.; 1H NMR (CD3OD, 250 MHz) δ 8.26 (d, 1H), 7.62-7.47 (c, 5H), 6.52 (d, 1H), 4.79 (s, 2H), 4.66 (q, 1H), 4.24 (br s, 1H), 3.90-3.80 (c, 2H), 2.95 (t, 2H), 2.70 (s, 3H), 1.49 (d, 3H); MS (APCI) 348 (MH+), [α]D+15.6 (c 1.0, MeOH).

後処理

  1. extractionextracted with ethyl acetate (4×)
  2. dry with materialThe combined organic extracts were dried over sodium sulfate
  3. filtrationfiltered
  4. customevaporated
  5. custompurified by flash column chromatography (2→5% methanol/ethyl acetate)
  6. customto give an oil which after titration with hexanes

出典と根拠

ORDレコード
ord-2f5172bcdfe14b93bdbbcec9261012be
出典データセット
uspto-grants-2005_08
特許番号
US06936600B2

反応ノート

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