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Hydrazine hydrate (1:1) → 6,7-dichloro-4-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)benzyl)phthalazin-1(2H)-one

HRID 1091749
ノート
印刷プレビュー

反応式

HRID 1091749 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[Cl:11])[C:7](=O)[O:6]/[C:5]/2=[CH:13]\[C:14]1[CH:19]=[CH:18][C:17]([F:20])=[C:16]([C:21]([N:23]2[CH2:28][CH2:27][CH:26]([O:29][CH3:30])[CH2:25][CH2:24]2)=[O:22])[CH:15]=1.O.[NH2:32][NH2:33]>O.CN(C)C=O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[Cl:11])[C:7](=[O:6])[NH:33][N:32]=[C:5]2[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[C:16]([C:21]([N:23]2[CH2:28][CH2:27][CH:26]([O:29][CH3:30])[CH2:25][CH2:24]2)=[O:22])[CH:15]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 2

HCID 24654Hydrazine hydrate (1:1)HCID 57791853(Z)-5,6-dichloro-3-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)benzylidene)isobenzofuran-1(3H)-one

生成物 1

HCID 577918676,7-dichloro-4-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)benzyl)phthalazin-1(2H)-one収率 35.4%

試薬・触媒・溶媒 2

HCID 962Water溶媒2 回HCID 6228
Dimethylformamide
溶媒

反応条件

温度
105 °C

実験手順

(Z)-5,6-dichloro-3-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)benzylidene)isobenzofuran-1(3H)-one (64) (127 mg, 0.28 mmol) was taken up in water (2 mL) and N,N-dimethylformamide (0.500 mL). The resulting mixture was treated with hydrazine hydrate (0.080 mL, 1.65 mmol) and the reaction was heated to 105° C. with stirring for 90 minutes. The reaction mixture was cooled, diluted with water (˜10 mL) and solid collected by suction filtration to afford the crude product, which was purified by flash silica chromatography, eluting with neat ethyl acetate. Pure fractions were evaporated to dryness and the residue triturated under diethyl ether and dried under vacuum to afford the desired material as a white solid (46.0 mg, 35% yield); 1H NMR (400.132 MHz, DMSO) δ 1.30-1.40 (1H, m), 1.44-1.53 (1H, m), 1.72-1.79 (1H, m), 1.87-1.94 (1H, m), 3.04-3.11 (1H, m), 3.29 (3H, s), 3.30-3.40 (2H, m), 3.44-3.49 (1H, m), 3.92-4.00 (1H, m), 4.37 (2H, s), 7.26 (1H, t), 7.38-7.45 (2H, m), 8.29 (1H, s), 8.40 (1H, s), 12.83 (1H, s); m/z (LC-MS, ESI+), RT=2.13 (M+H 464 & 465.9).

後処理

  1. temperatureThe reaction mixture was cooled
  2. filtrationcollected by suction filtration
  3. customto afford the crude product, which
  4. customwas purified by flash silica chromatography
  5. washeluting with neat ethyl acetate
  6. customPure fractions were evaporated to dryness
  7. customthe residue triturated under diethyl ether
  8. customdried under vacuum

出典と根拠

ORDレコード
ord-d759494d6627415ebcd86e342304eef7
出典データセット
uspto-grants-2012_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08129380B2

反応ノート

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