Water → tert-butyl 4-(2-{[5-(2-chloro-9-methyl-9H-purin-6-yl)-3-(trifluoromethyl)pyridin-2-yl]oxy}ethyl)piperidine-1-carboxylate

HRID 522283Notes

Reaction equation

HRID 522283 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH3:11])=[C:4](Cl)[N:3]=1.C([O-])([O-])=O.[Na+].[Na+].O.CC1(C)C(C)(C)OB([C:28]2[CH:29]=[C:30]([C:50]([F:53])([F:52])[F:51])[C:31]([O:34][CH2:35][CH2:36][CH:37]3[CH2:42][CH2:41][N:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:39][CH2:38]3)=[N:32][CH:33]=2)O1>O1CCOCC1.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>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH3:11])=[C:4]([C:28]2[CH:29]=[C:30]([C:50]([F:53])([F:51])[F:52])[C:31]([O:34][CH2:35][CH2:36][CH:37]3[CH2:42][CH2:41][N:40]([C:43]([O:45][C:46]([CH3:47])([CH3:48])[CH3:49])=[O:44])[CH2:39][CH2:38]3)=[N:32][CH:33]=2)[N:3]=1

Participants

7

Reactant 4

HCID 962Water2×HCID 10340Sodium CarbonateHCID 17125532,6-dichloro-9-methyl-9H-purineHCID 69931721Tert-butyl 4-(2-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluoromethyl)pyridin-2-yloxy)ethyl)piperidine-1-carboxylate

Product 1

HCID 117899621tert-butyl 4-(2-{[5-(2-chloro-9-methyl-9H-purin-6-yl)-3-(trifluoromethyl)pyridin-2-yl]oxy}ethyl)piperidine-1-carboxylateYield 63.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

2,6-Dichloro-9-methyl-9H-purine (5.6 g), Na2CO3 (11.7 g), water (16.8 mL), and tetrakis(triphenylphosphine)palladium (0) (1.6 g) were added to a solution of tert-butyl 4-(2-{[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluoromethyl)pyridin-2-yl]oxy}ethyl)piperidine-1-carboxylate (13.8 g) in dioxane (112 mL) at room temperature in an argon atmosphere, and the mixture was stirred at an internal temperature of 85° C. for 5 hours. After the reaction mixture was cooled to room temperature, water (700 mL) was added thereto, and the mixture was stirred for 3 hours. The precipitate was collected by filtration, then, washed with water and diisopropyl ether, and dried. The obtained solid was purified by silica gel column chromatography (Hex:EtOAc:CHCl3=1:1:1), whereby tert-butyl 4-(2-{[5-(2-chloro-9-methyl-9H-purin-6-yl)-3-(trifluoromethyl)pyridin-2-yl]oxy}ethyl)piperidine-1-carboxylate (9.5 g) was obtained as a solid.

Workup

  1. temperatureAfter the reaction mixture was cooled to room temperature
  2. stirringthe mixture was stirred for 3 hours
  3. filtrationThe precipitate was collected by filtration
  4. washwashed with water and diisopropyl ether
  5. customdried
  6. customThe obtained solid was purified by silica gel column chromatography (Hex:EtOAc:CHCl3=1:1:1)

Sources & evidence

ORD record
ord-82e9053cf2da4019886ee9e2c6ce64a2
Source dataset
uspto-grants-2016_05
Patent number
US09328118B2

Reaction notes

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