Pyridine → N-[4-(4-chlorophenyl)-1-oxophthalazin-2(1H)-yl]-2-[(1S,2S,5R)-3,3-difluoro-6,6-dimethylbicyclo[3.1.1]hept-2-yl]acetamide

HRID 469589노트

반응식

HRID 469589 반응식
[F:1][C:2]1([F:15])[CH2:7][C@H:6]2[CH2:8][C@H:4]([C:5]2([CH3:10])[CH3:9])[C@@H:3]1[CH2:11][C:12](Cl)=[O:13].[NH2:16][N:17]1[N:26]=[C:25]([C:27]2[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=2)[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:18]1=[O:34].N1C=CC=CC=1>C(Cl)(Cl)Cl>[Cl:33][C:30]1[CH:31]=[CH:32][C:27]([C:25]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:18](=[O:34])[N:17]([NH:16][C:12](=[O:13])[CH2:11][C@@H:3]3[C:2]([F:15])([F:1])[CH2:7][C@H:6]4[CH2:8][C@@H:4]3[C:5]4([CH3:10])[CH3:9])[N:26]=2)=[CH:28][CH:29]=1

참가 물질

5

반응물 3

HCID 1049PyridineHCID 671613672-amino-4-(4-chlorophenyl)phthalazin-1(2H)-oneHCID 866537462-((1S,2S,5R)-3,3-difluoro-6,6-dimethylbicyclo[3.1.1]heptan-2-yl)acetyl chloride

생성물 1

HCID 53239544N-[4-(4-chlorophenyl)-1-oxophthalazin-2(1H)-yl]-2-[(1S,2S,5R)-3,3-difluoro-6,6-dimethylbicyclo[3.1.1]hept-2-yl]acetamide

시약·촉매·용매 1

HCID 6212Chloroform용매

실험 절차

To a mixture of the above crude 2-((1S,2S,5R)-3,3-difluoro-6,6-dimethylbicyclo[3.1.1]heptan-2-yl)acetyl chloride (50 mg, 0.211 mmol) and the product from Example 86A (57.4 mg, 0.211 mmol) in 10 mL of CHCl3 was added pyridine (0.051 mL, 0.634 mmol). The reaction is stirred at rt for 12 hours and then reluxed for 16 hours, and quenched with 1M NaHCO3 (10 mL). The aq layer was extracted with EtOAc (2×20 mL), and the combined organic layers were dried (Na2SO4), filtered, and concentrated. The residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, 0-40% of EtOAc in hexanes). 1H NMR (300 MHz, DMSO-d6) δ ppm 11.51 (s, 1H), 8.39-8.43 (m, 1H), 7.94-8.00 (m, 2H), 7.70-7.76 (m, 1H), 7.58-7.70 (m, 4H), 2.92-3.09 (m, 1H), 2.81 (dd, J=15.3, 6.4 Hz, 1H), 2.36-2.45 (m, 3H), 2.11-2.16 (m, 1H), 1.93-2.04 (m, 1H), 1.27 (s, 3H), 1.08-1.20 (m, 2H), 1.01 (s, 3H); MS (ESI+) M/Z 472 (M+H)+.

후처리

  1. waitreluxed for 16 hours
  2. customquenched with 1M NaHCO3 (10 mL)
  3. extractionThe aq layer was extracted with EtOAc (2×20 mL)
  4. dry with materialthe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography

출처 및 근거

ORD 기록
ord-25057e2013a04c2ab6544895d81e37db
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08629143B2

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