Triethylamine → HCID 46178775, compound

HRID 2192668Notes

Reaction equation

HRID 2192668 reaction equation
Br[C:2]1[N:7]=[C:6]([C:8]([NH:10][C:11]2[CH:12]=[N:13][CH:14]=[CH:15][C:16]=2[C:17]2[CH2:22][CH:21]([CH3:23])[CH2:20][CH:19]([O:24][Si](C(C)(C)C)(C)C)[CH:18]=2)=[O:9])[CH:5]=[CH:4][C:3]=1[F:32].[F:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([F:40])[C:35]=1B(O)O.C(N(CC)CC)C>CCO.C1(C)C=CC=CC=1>[F:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([F:40])[C:35]=1[C:2]1[N:7]=[C:6]([C:8]([NH:10][C:11]2[CH:12]=[N:13][CH:14]=[CH:15][C:16]=2[C:17]2[CH2:22][CH:21]([CH3:23])[CH2:20][CH:19]([OH:24])[CH:18]=2)=[O:9])[CH:5]=[CH:4][C:3]=1[F:32]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27343362,6-Difluorophenylboronic acidHCID 59226530HCID 59226530, compound

Product 1

HCID 46178775HCID 46178775, compound

Reagents, catalysts & solvents 1

HCID 21863594Toluene ethanolSolvent

Procedure

A solution of 6-bromo-N-(4-(3-(tert-butyldimethylsilyloxy)-5-methylcyclohex-1-enyl)pyridin-3-yl)-5-fluoropicolinamide (1.0 equiv), 2,6-difluorophenyl boronic acid (3.0 equiv.), tetrakistriphenylphosphine (0.2 equiv.) and triethylamine (3.0 equiv.) in 1:1 EtOH/toluene (0.1 M) was heated at 120° C. with microwave irradiation for 1200 seconds. Upon cooling, removal of the volatiles in vacuo, the Suzuki product was directly purified by reverse phase HPLC. The product fraction was lyophilized and the resulting TBDMS ether was deprotected as described in Method 9 yielding, after RP HPLC purification and lyophilization, 6-(2,6-difluorophenyl)-5-fluoro-N-(4-(3-hydroxy-5-methylcyclohex-1-enyl)pyridin-3-yl)picolinamide as the TFA salt. LCMS (m/z): 438.2 (MH+); LC Rt=2.00 min.

Workup

  1. temperatureUpon cooling
  2. customremoval of the volatiles in vacuo
  3. customthe Suzuki product was directly purified by reverse phase HPLC
  4. customafter RP HPLC purification and lyophilization, 6-(2,6-difluorophenyl)-5-fluoro-N-(4-(3-hydroxy-5-methylcyclohex-1-enyl)pyridin-3-yl)picolinamide as the TFA salt

Sources & evidence

ORD record
ord-be74f3601c064b8b867092ea48ffdd11
Source dataset
uspto-grants-2012_12
Patent number
US08329732B2

Reaction notes

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