Triethylamine → (R)-1'-[2-(1-Butyryloxy-ethyl)-pyrimidin-4-yl]-6-chloro-spiro[chroman-2,4'-piperidin]-4-one

HRID 394514노트

반응식

HRID 394514 반응식
Cl.[Cl:2][C:3]1[CH:4]=[C:5]2[C:15](=[CH:16][CH:17]=1)[O:14][C:8]1([CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)[CH2:7][C:6]2=[O:18].[C:19]([O:24][C@@H:25]([C:27]1[N:32]=[C:31](Cl)[CH:30]=[CH:29][N:28]=1)[CH3:26])(=[O:23])[CH2:20][CH2:21][CH3:22].C(N(CC)CC)C>C(O)(C)C>[C:19]([O:24][C@@H:25]([C:27]1[N:28]=[C:29]([N:11]2[CH2:12][CH2:13][C:8]3([CH2:7][C:6](=[O:18])[C:5]4[C:15](=[CH:16][CH:17]=[C:3]([Cl:2])[CH:4]=4)[O:14]3)[CH2:9][CH2:10]2)[CH:30]=[CH:31][N:32]=1)[CH3:26])(=[O:23])[CH2:20][CH2:21][CH3:22]

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 10944226(R)-1-(4-chloro-pyrimidin-2-yl)ethyl butyrateHCID 223286586-Chlorospiro[chroman-2,4'-piperidin]-4-one hydrochloride

생성물 1

HCID 54550021(R)-1'-[2-(1-Butyryloxy-ethyl)-pyrimidin-4-yl]-6-chloro-spiro[chroman-2,4'-piperidin]-4-one수율 100%

시약·촉매·용매 1

HCID 3776Isopropanol용매

실험 절차

To a solution of 6-chloro-spiro[chroman-2,4′-piperidin]-4-one hydrochloride (prepared according to the method of Example 78, Step A, 175 mg, 0.61 mmol) in isopropanol (5 mL) was added (R)-1-(4-chloro-pyrimidin-2-yl)-ethyl butyrate (prepared according to the method of Preparation Seven, 160 mg, 0.70 mmol) followed by triethylamine (0.29 mL, 2.1 mmol). This mixture was stirred at reflux for 1.5 h, concentrated, and purified by flash column chromatography (1% methanol/chloroform) to give 270 mg (100%) of the title compound of Example 78, Step B as a yellow oil. 1H NMR (CDCl3, 400 MHz) δ 8.19 (d, 1H), 7.83 (d, 1H), 7.44 (dd, 1H), 6.97 (d, 1H), 6.37 (d, 1H), 5.64 (q, 1H), 4.18 (app s, 2H), 3.34 (t, 2H), 2.72 (s, 2H), 2.37 (t, 2H), 2.10 (d, 2H), 1.71-1.60 (c, 4H), 1.55 (d, 3H), 0.94 (t, 3H); MS (APCI) 444, 446 (MH+).

후처리

  1. customprepared
  2. customaccording to the method of Preparation Seven, 160 mg, 0.70 mmol)
  3. temperatureat reflux for 1.5 h
  4. concentrationconcentrated
  5. custompurified by flash column chromatography (1% methanol/chloroform)

출처 및 근거

ORD 기록
ord-468f3cb68d804616893ac760d47c9a20
출처 데이터셋
uspto-grants-2003_08
특허 번호
US06602875B2

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