3-Fluorobenzylamine → 4-chloro-7-(3-fluoro-benzylamino)-2H-phthalazin-1-one

HRID 1803547Notes

Reaction equation

HRID 1803547 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][N:6]=[C:5]2[Cl:13].BrC1C=C2C(C(Cl)=NNC2=O)=CC=1.[F:27][C:28]1[CH:29]=[C:30]([CH:33]=[CH:34][CH:35]=1)[CH2:31][NH2:32].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC([O-])(C)C.[Na+]>CC(N(C)C)=O.CCOC(C)=O>[Cl:13][C:5]1[C:4]2[C:9](=[CH:10][C:11]([NH:32][CH2:31][C:30]3[CH:33]=[CH:34][CH:35]=[C:28]([F:27])[CH:29]=3)=[CH:2][CH:3]=2)[C:8](=[O:12])[NH:7][N:6]=1

Participants

8

Reactant 5

HCID 668533-FluorobenzylamineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 533084876-Bromo-4-chlorophthalazin-1(2H)-oneHCID 674169997-bromo-4-chloro-2H-phthalazin-1-one

Product 1

HCID 249487234-chloro-7-(3-fluoro-benzylamino)-2H-phthalazin-1-one

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

A mixture 6-bromo-4-chloro-2H-phthalazin-1-one and 7-bromo-4-chloro-2H-phthalazin-1-one (150 mg, 0.58 mmol), 3-fluorobenzylamine (0.08 mL, 0.70 mmol), Pd-2(dba)3 (43 mg, 0.047 mmol), rac-BINAP (118 mg, 0.190 mmol) and NaOt-Bu (139 mg, 1.45 mmol) in DMA (8 mL) was heated at 80° C. for 40 min. The mixture was allowed to cool, diluted with EtOAc (25 mL) and washed with water (25 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated. Chromatography on silica (EtOAc/hexanes) afforded 4-chloro-7-(3-fluoro-benzylamino)-2H-phthalazin-1-one (32 mg) as a white solid, 1H (600 MHz, CDCl3) δ: 4.44 (s, 2H), 6.92 (m, 1H), 7.00 (d, 1H), 7.05 (dd, 1H), 7.08 (d, 1H), 7.26 (m, 1H), 7.37 (d, 1H), 7.71 (d, 1H), 10.40 (s, 1H) ppm. m/z (M+1) 303.97; 4-chloro-6-(3-fluoro-benzylamino)-2H-phthalazin-1-one (23 mg) as an off white solid, 1H (600 MHz, CDCl3) δ: 4.35 (s, 2H), 6.78 (d, 1H), 6.86 (m, 1H), 6.94 (dd, 1H), 6.97 (bd, 1H), 7.05 (d, 1H), 7.21 (m, 1H), 8.00 (d, 1H), 11.00 (s, 1H) ppm. m/z (M+1) 303.97.

Workup

  1. temperatureto cool
  2. washwashed with water (25 mL)
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-d9e7d4ab7655471ebee336cba18863a2
Source dataset
uspto-grants-2013_01
Patent number
US08349836B2

Reaction notes

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