Potassium Phosphate, Tribasic → tert-butyl 4-(4-(3-(1-(3,5-difluorobenzyl)-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-fluorophenyl)-5,6-di hydropyridine-1(2H)-carboxylate

HRID 531845Notes

Reaction equation

HRID 531845 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[CH:12]=[N:13][N:14]([CH2:16][C:17]4[CH:22]=[C:21]([F:23])[CH:20]=[C:19]([F:24])[CH:18]=4)[CH:15]=3)=[CH:9][N:8]([S:25]([C:28]3[CH:34]=[CH:33][C:31]([CH3:32])=[CH:30][CH:29]=3)(=[O:27])=[O:26])[C:5]2=[N:6][CH:7]=1.FC1C=C(C=C(F)C=1)CN1C=C(C2C3C(=NC=C(C4C=CC(OC)=C(NS(C)(=O)=O)C=4)C=3)NC=2)C=N1.[F:71][C:72]1[CH:77]=[C:76](B2OC(C)(C)C(C)(C)O2)[CH:75]=[CH:74][C:73]=1[C:87]1[CH2:92][CH2:91][N:90]([C:93]([O:95][C:96]([CH3:99])([CH3:98])[CH3:97])=[O:94])[CH2:89][CH:88]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:24][C:19]1[CH:18]=[C:17]([CH:22]=[C:21]([F:23])[CH:20]=1)[CH2:16][N:14]1[CH:15]=[C:11]([C:10]2[C:4]3[C:5](=[N:6][CH:7]=[C:2]([C:76]4[CH:75]=[CH:74][C:73]([C:87]5[CH2:92][CH2:91][N:90]([C:93]([O:95][C:96]([CH3:98])([CH3:97])[CH3:99])=[O:94])[CH2:89][CH:88]=5)=[C:72]([F:71])[CH:77]=4)[CH:3]=3)[N:8]([S:25]([C:28]3[CH:29]=[CH:30][C:31]([CH3:32])=[CH:33][CH:34]=3)(=[O:26])=[O:27])[CH:9]=2)[CH:12]=[N:13]1

Participants

8

Reactant 5

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 90031152tert-butyl 4-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate2×HCID 90031733N-(5-(3-(1-(3,5-difluorobenzyl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-methoxyphenyl)methanesulfonamideHCID 1182009805-bromo-3-(1-(3,5-difluorobenzyl)-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 118523940tert-butyl 4-(4-(3-(1-(3,5-difluorobenzyl)-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-fluorophenyl)-5,6-di hydropyridine-1(2H)-carboxylateYield 38.3%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

Using similar reaction conditions as described in step-i of example-1, 5-bromo-3-(1-(3,5-difluorobenzyl)-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine (step 1 product of example 71) (200 mg, 0.368 mmol) was coupled with tert-butyl 4-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate (intermediate 70) (296 mg, 0.736 mmol) using potassium phosphate (234 mg, 1.104 mmol), tricyclohexyl phosphine (15 mg, 0.055 mmol) and Pd2(dba)3 (34 mg, 0.036 mmol) in dioxane/water (15/3 ml) to afford 104 mg (38.3% yield) of the pure product after column purification using 35% ethyl acetate in hexane as eluent. MS: m/z=740.7 (M+1).

Workup

  1. customreaction conditions

Sources & evidence

ORD record
ord-17d716538c3a4c59b7d3823f37146655
Source dataset
uspto-grants-2016_05
Patent number
US09353107B2

Reaction notes

Loading…