Water → tert-Butyl 4-(4-[6-amino-5-[4-({[1-(2-fluoroethyl)-5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridin-3-yl]carbonyl}amino)phenyl]pyridin-3-yl]-1H-pyrazol-1-yl)piperidin-1-carboxylate

HRID 1428114Notes

Reaction equation

HRID 1428114 reaction equation
O.C(=O)([O-])[O-].[Cs+].[Cs+].[NH2:8][C:9]1[C:14]([C:15]2[CH:20]=[CH:19][C:18]([NH:21][C:22]([C:24]3[C:29](=[O:30])[C:28]([C:31]4[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=4)=[CH:27][N:26]([CH2:38][CH2:39][F:40])[CH:25]=3)=[O:23])=[CH:17][CH:16]=2)=[CH:13][C:12](Br)=[CH:11][N:10]=1.CC1(C)C(C)(C)OB([C:50]2[CH:51]=[N:52][N:53]([CH:55]3[CH2:60][CH2:59][N:58]([C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])[CH2:57][CH2:56]3)[CH:54]=2)O1>C(COC)OC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:8][C:9]1[N:10]=[CH:11][C:12]([C:50]2[CH:51]=[N:52][N:53]([CH:55]3[CH2:56][CH2:57][N:58]([C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])[CH2:59][CH2:60]3)[CH:54]=2)=[CH:13][C:14]=1[C:15]1[CH:20]=[CH:19][C:18]([NH:21][C:22]([C:24]2[C:29](=[O:30])[C:28]([C:31]3[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=3)=[CH:27][N:26]([CH2:38][CH2:39][F:40])[CH:25]=2)=[O:23])=[CH:17][CH:16]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 45480279tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylateHCID 86700059N-[4-(2-Amino-5-bromopyridin-3-yl)phenyl]-1-(2-fluoroethyl)-5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxamide

Product 1

HCID 86700067tert-Butyl 4-(4-[6-amino-5-[4-({[1-(2-fluoroethyl)-5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridin-3-yl]carbonyl}amino)phenyl]pyridin-3-yl]-1H-pyrazol-1-yl)piperidin-1-carboxylateYield 120.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

Water (0.5 ml), cesium carbonate (60 mg) and tetrakis(triphenylphosphine)palladium (16 mg) were added to a solution of the compound obtained in Step 1 of Example 43 (75 mg) and tert-butyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylate (59 mg) in dimethoxyethane (4 ml). The mixture was stirred under microwave irradiation at 100° C. for 10 minutes. After leaving to cool, the reaction product was purified by silica gel column chromatography [chloroform:methanol=99:1->9:1 (v/v)]. Further, the resulting crude purified product was crystallized from ethyl acetate to give 120 mg of the title compound as a solid.

Workup

  1. customAfter leaving
  2. temperatureto cool
  3. customthe reaction product was purified by silica gel column chromatography [chloroform:methanol=99:1->9:1 (v/v)]
  4. customFurther, the resulting crude purified product
  5. customwas crystallized from ethyl acetate

Sources & evidence

ORD record
ord-8775bf1d90af429b80ee03232f0c8f24
Source dataset
uspto-grants-2015_01
Patent number
US08933103B2

Reaction notes

Loading…