Potassium Phosphate, Tribasic → HCID 66743216, compound

HRID 1431056Notes

Reaction equation

HRID 1431056 reaction equation
Cl[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[N:16]=[CH:15][C:14]([N:17]3[C@H:22]4[CH2:23][CH2:24][C@@H:18]3[CH2:19][N:20]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21]4)=[CH:13][CH:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1.[C:32]([O:35][CH2:36][C:37]1[C:42](B2OC(C)(C)C(C)(C)O2)=[CH:41][CH:40]=[CH:39][C:38]=1[N:52]1[N:61]=[CH:60][C:59]2[C:54](=[C:55]([F:66])[CH:56]=[C:57]([C:62]([CH3:65])([CH3:64])[CH3:63])[CH:58]=2)[C:53]1=[O:67])(=[O:34])[CH3:33].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+]>O1CCOCC1.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:32]([O:35][CH2:36][C:37]1[C:38]([N:52]2[N:61]=[CH:60][C:59]3[C:54](=[C:55]([F:66])[CH:56]=[C:57]([C:62]([CH3:64])([CH3:63])[CH3:65])[CH:58]=3)[C:53]2=[O:67])=[CH:39][CH:40]=[CH:41][C:42]=1[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[N:16]=[CH:15][C:14]([N:17]3[CH:22]4[CH2:23][CH2:24][CH:18]3[CH2:19][N:20]([C:25]([O:27][C:28]([CH3:29])([CH3:30])[CH3:31])=[O:26])[CH2:21]4)=[CH:13][CH:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1)(=[O:34])[CH3:33]

Participants

7

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 66742735HCID 66742735, compound

Product 1

HCID 66743216HCID 66743216, compoundYield 60.3%

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

This reaction was carried out under similar conditions to those described above in step 7 of preparation of Example 6. (1R,5S)-tert-butyl 8-(6-(6-chloro-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)-3,8-diazabicyclo[3.2.1]octane-3-carboxylate (100 mg, 224 umol), 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetate (114 mg, 224 umol), xPhos (10.7 mg, 22.4 umol) and potassium phosphate (119 mg, 559 umol) in 7 ml of Dioxane/water (9:1) was degassed with nitrogen for 10 minutes and bis(dibenzylideneacetone)palladium (0) (6.42, 11.2 umol) was added. The reaction mixture was heated to 100° C. for 2 hr. After work up, the product was purified by preparative HPLC on silica gel, using a gradient of 5% to 70% ethylacetate/hexane. This provided the desired product as a light yellow solid (105 mg 60.3%). (M+H)+=779 m/e.

Workup

  1. customthose described above in step 7 of preparation of Example 6
  2. customAfter work up, the product was purified by preparative HPLC on silica gel

Sources & evidence

ORD record
ord-f3a3225ff7ff4cd4aee7aa56ded4d229
Source dataset
uspto-grants-2015_01
Patent number
US08940741B2

Reaction notes

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