3-(Trifluoromethoxy)benzylamine → 4-chloro-7-(3-trifluoromethoxy-benzylamino)-2H-phthalazin-1-one

HRID 1803548Notes

Reaction equation

HRID 1803548 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]([F:39])([F:38])[O:29][C:30]1[CH:31]=[C:32]([CH:35]=[CH:36][CH:37]=1)[CH2:33][NH2:34].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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:13][C:5]1[C:4]2[C:9](=[CH:10][C:11]([NH:34][CH2:33][C:32]3[CH:35]=[CH:36][CH:37]=[C:30]([O:29][C:28]([F:27])([F:38])[F:39])[CH:31]=3)=[CH:2][CH:3]=2)[C:8](=[O:12])[NH:7][N:6]=1

Participants

9

Reactant 5

HCID 1452643-(Trifluoromethoxy)benzylamineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 533084876-Bromo-4-chlorophthalazin-1(2H)-oneHCID 674169997-bromo-4-chloro-2H-phthalazin-1-one

Product 1

HCID 584473154-chloro-7-(3-trifluoromethoxy-benzylamino)-2H-phthalazin-1-one

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 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-(trifluoromethoxy)benzylamine (0.08 mL, 0.636 mmol), Pd2(dba)3 (61 mg, 0.0667 mmol), rac-BINAP (120 mg, 0.193 mmol) and NaOt-Bu (155 mg, 1.613 mmol) in DMA (8 mL) was heated at 80° C. for 1 h. The mixture was allowed to cool. The mixture was allowed to cool, diluted with EtOAc and washed with water. The organic layer was washed with sat.aq. NaHCO3, brine and dried (Na2SO4). Chromatography on silica (EtOAc/hexanes) afforded 4-chloro-7-(3-trifluoromethoxy-benzylamino)-2H-phthalazin-1-one (28 mg) as an off white solid, 1H (600 MHz, CDCl3) δ: 4.50 (s, 2H), 7.06 (dd, 1H), 7.14 (d, 1H), 7.18 (s, 1H), 7.28 (d, 1H), 7.38 (t, 1H), 7.44 (d, 1H), 7.78 (d, 1H), 9.48 (s, 1H), m/z (M+1) 369.93; 4-chloro-6-(3-trifluoromethoxy-benzylamino)-2H-phthalazin-1-one (22 mg) as an off white solid, 1H (600 MHz, CDCl3) δ: 4.41 (s, 2H), 6.83 (d, 1H), 6.98 (dd, 1H), 7.08 (bd, 1H), 7.16 (bs, 1H), 7.25 (s, 1H), 7.32 (t, 1H), 8.06 (d, 1H), 10.15 (s, 1H) ppm. m/z (M+1) 369.93.

Workup

  1. temperatureto cool
  2. temperatureto cool
  3. washwashed with water
  4. washThe organic layer was washed with sat.aq
  5. dry with materialNaHCO3, brine and dried (Na2SO4)

Sources & evidence

ORD record
ord-653c5837da534c2d8a2d6f8096dc81f2
Source dataset
uspto-grants-2013_01
Patent number
US08349836B2

Reaction notes

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