Triethylamine → (R)-Tetrahydrofuran-3-yl((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-3-yl)methylcarbamate

HRID 2079355노트

반응식

HRID 2079355 반응식
[NH2:1][CH2:2][C@@H:3]1[CH2:8][CH2:7][CH2:6][N:5]([C:9]2[C:18]3[C:13](=[CH:14][C:15]([CH3:19])=[CH:16][CH:17]=3)[N:12]=[C:11]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[OH:26])[N:10]=2)[CH2:4]1.Cl[C:28]([O:30][C@@H:31]1[CH2:35][CH2:34][O:33][CH2:32]1)=[O:29].C(N(CC)CC)C>CN(C=O)C>[OH:26][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[C:11]1[N:10]=[C:9]([N:5]2[CH2:6][CH2:7][CH2:8][C@@H:3]([CH2:2][NH:1][C:28](=[O:29])[O:30][C@@H:31]3[CH2:35][CH2:34][O:33][CH2:32]3)[CH2:4]2)[C:18]2[C:13](=[CH:14][C:15]([CH3:19])=[CH:16][CH:17]=2)[N:12]=1

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 58089797(3R)-oxolan-3-yl carbonochloridateHCID 1361213552-(4-((S)-3-(Aminomethyl)piperidin-1-yl)-7-methylquinazolin-2-yl)phenol

생성물 1

HCID 136121430(R)-Tetrahydrofuran-3-yl((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-3-yl)methylcarbamate

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

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온도
0 °C

실험 절차

2-(4-((S)-3-(Aminomethyl)piperidin-1-yl)-7-methylquinazolin-2-yl)phenol (127 mg, 0.364 mmol) was dissolved in 5 mL anhydrous DMF and cooled to 0° C., and a solution of (R)-tetrahydrofuran-3-yl chloroformate (65.4 mg, 0.436 mmol) in 200 μL DMF was added dropwise followed by the addition of triethylamine (74 mg, 0.10 mL, 0.73 mmol). The reaction was allowed to warm to room temperature. The reaction was complete after two hours. The mixture was partitioned between H2O and CH2Cl2, and separated, and the aqueous layer was extracted twice with CH2Cl2. The combined organic phases were dried over Na2SO4, filtered, and concentrated to a yellow solid. Purification via silica gel chromatography using 98% CH2Cl2/2% MeOH gave (R)-tetrahydrofuran-3-yl ((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-3-yl)methylcarbamate as an off white solid (116 mg, 69%). LC/MS: m/z 463.5 (M+H)+ at 2.37 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

후처리

  1. temperatureto warm to room temperature
  2. customThe mixture was partitioned between H2O and CH2Cl2
  3. customseparated
  4. extractionthe aqueous layer was extracted twice with CH2Cl2
  5. dry with materialThe combined organic phases were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to a yellow solid
  8. customPurification via silica gel chromatography

출처 및 근거

ORD 기록
ord-4889f65193db40239c2e8584234a3865
출처 데이터셋
uspto-grants-2011_04
특허 번호
US07928107B2

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