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

HRID 1091749Notes

Reaction equation

HRID 1091749 reaction equation
[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

Participants

5

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
105 °C

Procedure

(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).

Workup

  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

Sources & evidence

ORD record
ord-d759494d6627415ebcd86e342304eef7
Source dataset
uspto-grants-2012_03
Patent number
US08129380B2

Reaction notes

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