Triethylamine → HCID 46178775, compound

HRID 2046892Notes

Reaction equation

HRID 2046892 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-methyl-cyclohex-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-e397624578b147d8bbf124022168cdf1
Source dataset
uspto-grants-2013_11
Patent number
US08592455B2

Reaction notes

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