Toluene → N-[2-fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]-2-methylsuccinamic acid

HRID 459769

반응식

HRID 459769 반응식
[NH2:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][C:19]=1[F:20])[CH2:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9](=[O:16])[NH:8][N:7]=1.[CH3:21][CH:22]1[CH2:26][C:25](=[O:27])[O:24][C:23]1=[O:28].C1(C)C=CC=CC=1>O>[F:20][C:19]1[CH:18]=[CH:17][C:4]([CH2:5][C:6]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9](=[O:16])[NH:8][N:7]=2)=[CH:3][C:2]=1[NH:1][C:25](=[O:27])[CH2:26][CH:22]([CH3:21])[C:23]([OH:28])=[O:24]

참가 물질

5

반응물 3

HCID 1140TolueneHCID 20051Methylsuccinic anhydrideHCID 184443734-(3-amino-4-fluorobenzyl)-2H-phthalazin-1-one

생성물 1

HCID 18444382N-[2-fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]-2-methylsuccinamic acid

시약·촉매·용매 1

HCID 962Water용매

실험 절차

A stirred mixture of 4-(3-amino-4-fluorobenzyl)-2H-phthalazin-1-one (2.02 g, 7.5 mmol; prepared in a manner similar to that described in Example 23), 3-methyldihydrofuran-2,5-dione (0.856 g, 7.5 mmol) and toluene (100 ml) was heated under reflux for 2.5 hours (for the first 30 minutes of this period, traces of water in the mixture were removed by azeotropic distillation). The resulting solid was collected by filtration from the hot mixture, washed with toluene (20 ml) and dried in vacuo to give N-[2-fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]-2-methylsuccinamic acid (1.91 g) as an off-white solid, m.pt. 140–144° C.; 250 MHz 1H-nmr (d6-DMSO) δ (ppm): 0.95 (d, 3H) (CH3), 2.2–2.6 (m, 3H) (—CH2CHMe-), 4.1 (s, 2H) (ArCH2—), 6.9–7.2 (m, 2H) (2×ArH), 7.6–7.9 (m, 4H) (4×ArH), 8.1 (d, 1H) (ArH), 9.55 (s, 1H) (chain CONH), 12.0 (br s, 1H) (CO2H), 12.5 (s, 1H) (ring CONH); m/z (M+H)+ 384, 100% purity.

후처리

  1. customprepared in a manner similar to
  2. temperaturewas heated
  3. temperatureunder reflux for 2.5 hours (for the first 30 minutes of this period
  4. customwere removed by azeotropic distillation)
  5. filtrationThe resulting solid was collected by filtration from the hot mixture
  6. washwashed with toluene (20 ml)
  7. customdried in vacuo

출처 및 근거

ORD 기록
ord-b7b52a9354ba48a7bcbbaae69407a098
출처 데이터셋
uspto-grants-2007_03
특허 번호
US07196085B2

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