Sodium Carbonate → HCID 178495955, compound

HRID 1623349Notes

Reaction equation

HRID 1623349 reaction equation
FC(F)(F)C(O)=O.[NH2:8][C@H:9]1[CH2:14][CH2:13][C@H:12]([NH:15][C:16]2[CH:21]=[C:20]([C:22]3[C:27]([F:28])=[CH:26][CH:25]=[C:24]([NH:29][CH2:30][CH:31]4[CH2:36][CH2:35][O:34][CH2:33][CH2:32]4)[N:23]=3)[C:19]([Cl:37])=[CH:18][N:17]=2)[CH2:11][CH2:10]1.C(=O)([O-])[O-].[Na+].[Na+].[CH3:44][O:45][CH2:46][CH2:47]OS(C1C=CC(C)=CC=1)(=O)=O>CS(C)=O>[Cl:37][C:19]1[C:20]([C:22]2[C:27]([F:28])=[CH:26][CH:25]=[C:24]([NH:29][CH2:30][CH:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)[N:23]=2)=[CH:21][C:16]([NH:15][C@H:12]2[CH2:13][CH2:14][C@H:9]([NH:8][CH2:47][CH2:46][O:45][CH3:44])[CH2:10][CH2:11]2)=[N:17][CH:18]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 86977Ethanol, 2-methoxy-, 1-(4-methylbenzenesulfonate)HCID 178511607HCID 178511607, compound

Product 1

HCID 178495955HCID 178495955, compoundYield 18.5%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
85 °C

Procedure

To a mixture of N2′-(trans-4-aminocyclohexyl)-5′-chloro-3-fluoro-N6-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine trifluoroacetate (30 mg, 0.055 mmol) and sodium carbonate (23 mg, 0.22 mmol) in DMSO (0.75 ml) was added p-toluenesulfonic acid 2-methoxyethyl ester (15 mg, 0.066 mmol). The mixture was stirred at 85° C. for 20 hr in a sealed microwave vial. The cooled reaction mixture was filtered. The filtrate was purified by reverse phase HPLC and lyophilized to give 5.0 mg of 5′-chloro-3-fluoro-N2′-(trans-4-(2-methoxyethylamino)cyclohexyl)-N6-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine as its TFA salt. LCMS (m/z): 492.2 (MH+), retention time=0.57 min.; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.10-1.46 (m, 6H) 1.64-1.74 (m, 2H) 1.86 (br. s., 2H) 1.95-2.09 (m, 2H) 2.09-2.26 (m, 2H) 2.58 (br. s., 1H) 2.88 (t, J=5.09 Hz, 2H) 3.17 (t, J=6.26 Hz, 2H) 3.29-3.45 (m, 5H) 3.53 (t, J=5.09 Hz, 3H) 4.00 (dd, J=11.35, 3.52 Hz, 2H) 4.34-4.47 (m, 1H) 4.54-4.68 (m, 1H) 6.35-6.48 (m, 2H) 7.31 (t, J=8.80 Hz, 1H) 8.11 (s, 1H).

Workup

  1. customThe cooled reaction mixture
  2. filtrationwas filtered
  3. customThe filtrate was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-302059d9dfda47e0af017139fff2c77b
Source dataset
uspto-grants-2014_07
Patent number
US08778951B2

Reaction notes

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