Triethylamine → [1-(3-Benzyloxy-1-cyclopropyl-6-fluoro-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-7-yl)-azetidin-3-yl]-carbamic acid tert-butyl ester

HRID 2270239노트

반응식

HRID 2270239 반응식
[CH2:1]([O:8][N:9]1[C:18](=[O:19])[C:17]2[C:12](=[CH:13][C:14](Cl)=[C:15]([F:20])[CH:16]=2)[N:11]([CH:22]2[CH2:24][CH2:23]2)[C:10]1=[O:25])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:26]([O:30][C:31](=[O:37])[NH:32][CH:33]1[CH2:36][NH:35][CH2:34]1)([CH3:29])([CH3:28])[CH3:27].C(N(CC)CC)C>CC(N(C)C)=O.O>[C:26]([O:30][C:31](=[O:37])[NH:32][CH:33]1[CH2:36][N:35]([C:14]2[CH:13]=[C:12]3[C:17]([C:18](=[O:19])[N:9]([O:8][CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)[C:10](=[O:25])[N:11]3[CH:22]3[CH2:24][CH2:23]3)=[CH:16][C:15]=2[F:20])[CH2:34]1)([CH3:29])([CH3:27])[CH3:28]

참가 물질

6

반응물 3

HCID 8471TriethylamineHCID 15194053-Aminoazetidine, 3-BOC protectedHCID 226328893-Benzyloxy-7-chloro-1-cyclopropyl-6-fluoro-1H-quinazoline-2,4-dione

생성물 1

HCID 54491769[1-(3-Benzyloxy-1-cyclopropyl-6-fluoro-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-7-yl)-azetidin-3-yl]-carbamic acid tert-butyl ester수율 47.6%

시약·촉매·용매 2

HCID 962Water용매HCID 31374Dimethylacetamide용매

반응 조건

온도
80 °C

실험 절차

A solution of 3-benzyloxy-7-chloro-1-cyclopropyl-6-fluoro-1H-quinazoline-2,4dione (Example E-3, 0.20 g, 0.55 mmol) in DMA (3.0 mL) was reacted with azetidin-3-yl-carbamic acid tert-butyl ester (0.286 g, 1.66 mmol), triethylamine (0.76 mL, 5.5 mmol) and heated to 80° C. for 2 days. The mixture was then cooled, diluted with H2O, and extracted with ethyl acetate. The organic layers were combined, dried with sodium sulfate, and concentrated. The residue was purified by column chromatography (silica gel, 3:1 hexanes/ethyl acetate to 1:1 hexanes/ethyl acetate) to provide 0.13 g of the title compound as a solid.

후처리

  1. temperatureThe mixture was then cooled
  2. extractionextracted with ethyl acetate
  3. dry with materialdried with sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography (silica gel, 3:1 hexanes/ethyl acetate to 1:1 hexanes/ethyl acetate)

출처 및 근거

ORD 기록
ord-08d43889e78942639aa156feb7c20117
출처 데이터셋
uspto-grants-2001_12
특허 번호
US06331538B1

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