Dichloromethane → tert-butyl 5'-chloro-2'-fluoro-2,4'-bipyridin-6-yl((4-methoxytetrahydro-2H-pyran-4-yl)methyl)carbamate

HRID 1623262Notes

Reaction equation

HRID 1623262 reaction equation
Br[C:2]1[N:7]=[C:6]([N:8]([CH2:16][C:17]2([O:23][CH3:24])[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH:5]=[CH:4][CH:3]=1.[Cl:25][C:26]1[C:27](B(O)O)=[CH:28][C:29]([F:32])=[N:30][CH:31]=1.C(Cl)Cl.COCCOC>CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:25][C:26]1[C:27]([C:2]2[CH:3]=[CH:4][CH:5]=[C:6]([N:8]([CH2:16][C:17]3([O:23][CH3:24])[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)[C:9](=[O:15])[O:10][C:11]([CH3:13])([CH3:14])[CH3:12])[N:7]=2)=[CH:28][C:29]([F:32])=[N:30][CH:31]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 80711,2-DimethoxyethaneHCID 44754822(5-Chloro-2-fluoropyridin-4-yl)boronic acidHCID 58127385tert-butyl 6-bromopyridin-2-yl((4-methoxytetrahydro-2H-pyran-4-yl)methyl)carbamate

Product 1

HCID 58127426tert-butyl 5'-chloro-2'-fluoro-2,4'-bipyridin-6-yl((4-methoxytetrahydro-2H-pyran-4-yl)methyl)carbamateYield 57%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of tert-butyl 6-bromo-pyridin-2-yl((4-methoxytetrahydro-2H-pyran-4-yl)methyl)carbamate (50 mg, 0.125 mmol), 5-chloro-2-fluoropyridin-4-ylboronic acid (43.7 mg, 0.249 mmol), PdCl2(dppf).CH2Cl2 adduct (15.2 mg, 0.019 mmol), DME (1.5 Ml) and 2M aqueous Na2CO2 (0.25 Ml, 0.5 mmol) was sealed and stirred at 100° C. for 3 hours. After cooling to room temperature the mixture was diluted with EtOAc (15 Ml), filtered and concentrated in vacuo. The crude material was purified by column chromatography [silica gel, 12 g, EtOAc/hexane=5/100 to 50/50] to provide tert-butyl 5′-chloro-2′-fluoro-2,4′-bipyridin-6-yl((4-methoxytetrahydro-2H-pyran-4-yl)methyl)carbamate (32 mg, 57% yield). LCMS (m/z): 452.2 [M+H]+; retention time=1.068 min.

Workup

  1. temperatureAfter cooling to room temperature the mixture
  2. filtrationfiltered
  3. concentrationconcentrated in vacuo
  4. customThe crude material was purified by column chromatography [silica gel, 12 g, EtOAc/hexane=5/100 to 50/50]

Sources & evidence

ORD record
ord-04496030a0b941b79f25df55f93c4892
Source dataset
uspto-grants-2014_07
Patent number
US08778951B2

Reaction notes

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