Potassium Carbonate → HCID 178428217, compound

HRID 2283498Notes

Reaction equation

HRID 2283498 reaction equation
C(=O)([O-])[O-].[K+].[K+].[OH:7][CH2:8][C@H:9]1[CH2:14][CH2:13][C@H:12]([C:15]([O:17]C)=[O:16])[CH2:11][CH2:10]1.F[C:20]1[N:25]=[CH:24][C:23]([C:26]2[CH:31]=[C:30]([CH3:32])[CH:29]=[C:28]([NH:33][C:34]3[CH:39]=[C:38]([C:40]([F:43])([F:42])[F:41])[CH:37]=[CH:36][N:35]=3)[N:27]=2)=[CH:22][CH:21]=1.CCN(C(C)C)C(C)C.[OH-].[Na+]>CN1C(=O)CCC1>[CH3:32][C:30]1[CH:29]=[C:28]([NH:33][C:34]2[CH:39]=[C:38]([C:40]([F:43])([F:42])[F:41])[CH:37]=[CH:36][N:35]=2)[N:27]=[C:26]([C:23]2[CH:24]=[N:25][C:20]([O:7][CH2:8][C@H:9]3[CH2:10][CH2:11][C@H:12]([C:15]([OH:17])=[O:16])[CH2:13][CH2:14]3)=[CH:21][CH:22]=2)[CH:31]=1

Participants

7

Reactant 5

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 71469032HCID 71469032, compoundHCID 178501147HCID 178501147, compound

Product 1

HCID 178428217HCID 178428217, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
130 °C

Procedure

A flask was charged with potassium carbonate (0.028 g, 0.200 mmol), methyl trans-4-(hydroxymethyl)cyclohexanecarboxylate (0.034 g, 0.200 mmol), 6′-fluoro-4-methyl-N-[4-(trifluoromethyl)pyridin-2-yl]-2,3′-bipyridin-6-amine (0.032 g, 0.1 mmol), NMP (1 mL), and DIEA (0.035 mL, 0.20 mmol). The vial was sealed and heated to 130° C. for 72 hours. Aqueous NaOH (1M, 0.5 mL) was added, and the vial was heated in a microwave for 10 minutes at 110° C. The mixture was filtered through a CELITE cartridge, washing with NMP (3 mL). The residue, dissolved in 3 mL of NMP, was purified by mass triggered reverse phase HPLC (21-55% Acetonitrile/Water with a 0.1% Ammonium Hydroxide modifier on a Waters X-Bridge C18 19 mm×100 mm) to yield trans-4-{[(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}-2,3′-bipyridin-6′-yl)oxy]methyl}cyclohexanecarboxylic acid. MS ESI calcd. for C25H26F3N4O3 [M+H]+ 487. found 487. rhSyk IC50=3 nM.

Workup

  1. customThe vial was sealed
  2. temperaturethe vial was heated in a microwave for 10 minutes at 110° C
  3. filtrationThe mixture was filtered through a CELITE cartridge
  4. washwashing with NMP (3 mL)
  5. dissolutionThe residue, dissolved in 3 mL of NMP
  6. customwas purified by mass triggered reverse phase HPLC (21-55% Acetonitrile/Water with a 0.1% Ammonium Hydroxide modifier on a Waters X-Bridge

Sources & evidence

ORD record
ord-27088733435f4ad69e41f1483a7500cc
Source dataset
uspto-grants-2015_09
Patent number
US09145391B2

Reaction notes

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