Potassium Phosphate, Tribasic → HCID 66742743, compound

HRID 1431046Notes

Reaction equation

HRID 1431046 reaction equation
Cl[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([CH2:17][N:18]3[CH2:21][CH:20]([O:22][CH3:23])[CH2:19]3)=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1.[C:24]([C:28]1[CH:29]=[C:30]2[C:35](=[C:36]([F:38])[CH:37]=1)[C:34](=[O:39])[N:33]([C:40]1[CH:50]=[CH:49][CH:48]=[C:47](B3OC(C)(C)C(C)(C)O3)[C:41]=1[CH2:42][O:43][C:44](=[O:46])[CH3:45])[N:32]=[CH:31]2)([CH3:27])([CH3:26])[CH3:25].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>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:24]([C:28]1[CH:29]=[C:30]2[C:35](=[C:36]([F:38])[CH:37]=1)[C:34](=[O:39])[N:33]([C:40]1[CH:50]=[CH:49][CH:48]=[C:47]([C:2]3[CH:3]=[C:4]([NH:10][C:11]4[CH:16]=[CH:15][C:14]([CH2:17][N:18]5[CH2:21][CH:20]([O:22][CH3:23])[CH2:19]5)=[CH:13][N:12]=4)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=3)[C:41]=1[CH2:42][O:43][C:44](=[O:46])[CH3:45])[N:32]=[CH:31]2)([CH3:25])([CH3:26])[CH3:27]

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 594737692-(6-(tert-Butyl)-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetateHCID 66742887HCID 66742887, compound

Product 1

HCID 66742743HCID 66742743, compoundYield 92%

Reagents, catalysts & solvents 1

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalyst

Conditions

Temperature
110 °C

Procedure

6-Chloro-4-[5-(3-methoxy-azetidin-1-ylmethyl)-pyridin-2-ylamino]-2-methyl-2H-pyridazin-3-one (100 mg, 0.29 mmol, Eq: 1.0), acetic acid 2-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl ester (247 mg, 0.5 mmol, Eq: 1.75), bis(dibenzylideneacetone)palladium (8.2 mg, 0.014 mmol, Eq: 0.05), x-phos (13.6 mg, 0.028 mmol, Eq: 0.10), and tripotassium phosphate (121 mg, 0.57 mmol, Eq: 2.0) were added to a microwave vial. The vial was capped and purged with nitrogen. Butanol (2.3 ml) and water (0.5 ml) were added and the vial was purged again, then backfilled with nitrogen. The reaction was heated at 110° C. for 2.5 hrs in a sand bath. The crude reaction was filtered through celite and purified by chromatography using a gradient of 0% to 25% methanol in DCM. Fractions containing the desired product were combined with those in which the acetate protecting group had been removed during the course of the reaction to give 175 mg of material (approximately 92%).

Workup

  1. customThe vial was capped
  2. custompurged with nitrogen
  3. additionButanol (2.3 ml) and water (0.5 ml) were added
  4. customthe vial was purged again
  5. customThe crude reaction
  6. filtrationwas filtered through celite
  7. custompurified by chromatography
  8. additionFractions containing the desired product
  9. customhad been removed during the course of the reaction

Sources & evidence

ORD record
ord-ca24b74b0f19489495d451ca249e98a6
Source dataset
uspto-grants-2015_01
Patent number
US08940741B2

Reaction notes

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