Sodium Hydroxide → 6-tert-Butyl-8-fluoro-2-{2-hydroxymethyl-3-[1-methyl-5-(4-methyl-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-5'-ylamino)-6-oxo-1,6-dihydro-pyridazin-3-yl]-phenyl}-2H-phthalazin-1-one

HRID 449635

Reaction equation

HRID 449635 reaction equation
Cl[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[N:12]=[CH:13][C:14]([N:17]3[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]3)=[N:15][CH:16]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1.C([O:27][CH2:28][C:29]1[C:34]([N:35]2[N:44]=[CH:43][C:42]3[C:37](=[C:38]([F:49])[CH:39]=[C:40]([C:45]([CH3:48])([CH3:47])[CH3:46])[CH:41]=3)[C:36]2=[O:50])=[CH:33][CH:32]=[CH:31][C:30]=1[B-](F)(F)F)(=O)C.[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[OH-].[Na+]>C(O)CCC.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.[Pd]>[C:45]([C:40]1[CH:41]=[C:42]2[C:37](=[C:38]([F:49])[CH:39]=1)[C:36](=[O:50])[N:35]([C:34]1[CH:33]=[CH:32][CH:31]=[C:30]([C:2]3[CH:3]=[C:4]([NH:10][C:11]4[N:12]=[CH:13][C:14]([N:17]5[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]5)=[N:15][CH:16]=4)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=3)[C:29]=1[CH2:28][OH:27])[N:44]=[CH:43]2)([CH3:48])([CH3:46])[CH3:47]

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 667424166-chloro-2-methyl-4-(4-methyl-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-5'-ylamino)-2H-pyridazin-3-oneHCID 87134390potassium (2-(acetoxymethyl)-3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)phenyl)trifluoroborate

Product 1

HCID 566558906-tert-Butyl-8-fluoro-2-{2-hydroxymethyl-3-[1-methyl-5-(4-methyl-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-5'-ylamino)-6-oxo-1,6-dihydro-pyridazin-3-yl]-phenyl}-2H-phthalazin-1-one

Reagents, catalysts & solvents 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 2631-ButanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
110 °C

Procedure

To a 15 mL microwave reaction vial was added 6-chloro-2-methyl-4-(4-methyl-3,4,5,6-tetrahydro-2H-[1,2]bipyrazinyl-5′-ylamino)-2H-pyridazin-3-one (71 mg, 211 μmol, Eq: 1.00) in 7 mL n-butanol and 1.4 mL water. Argon was bubbled through the suspension. To the slurry was added potassium (2-(acetoxymethyl)-3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)phenyl)trifluoroborate (149 mg, 211 μmol, Eq: 1.00), then X-PHOS (15.1 mg, 31.7 μmol, Eq: 0.15) with stirring. To this mixture was added bis(dibenzylideneacetone)palladium (9.12 mg, 15.9 μmol, Eq: 0.075). The tube was sealed and heated at 110° C. (bath temp) for 3 hrs then cooled to room temperature. A solution of NaOH (84 mg, 2.11 mmol, 10 eq) in water (1.5 mL) was added and the reaction was stirred for 3 days.

Workup

  1. customTo a 15 mL microwave reaction
  2. customArgon was bubbled through the suspension
  3. customThe tube was sealed
  4. temperaturethen cooled to room temperature

Sources & evidence

ORD record
ord-4fb3aa557ef84c0ea937c3d9683c5ae5
Source dataset
uspto-grants-2013_07
Patent number
US08481540B2

Linked notes

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