Cyclohexanecarboxylic acid → HCID 86704199, compound

HRID 1497658Notes

Reaction equation

HRID 1497658 reaction equation
[CH:1]1([C:7]([OH:9])=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:10](Cl)(=[O:14])[C:11](Cl)=O.[NH2:16][C:17]1[S:18][C:19]([C:45]2[CH:50]=[CH:49][N:48]=[CH:47][CH:46]=2)=[C:20]([C:22]2[C:23]([F:44])=[C:24]([N:29]([CH2:41][O:42][CH3:43])[S:30]([C:33]3[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=3[F:40])(=[O:32])=[O:31])[CH:25]=[CH:26][C:27]=2[F:28])[N:21]=1>C(Cl)Cl>[CH:11]1([C:10]([N:16]([C:17]2[S:18][C:19]([C:45]3[CH:46]=[CH:47][N:48]=[CH:49][CH:50]=3)=[C:20]([C:22]3[C:27]([F:28])=[CH:26][CH:25]=[C:24]([N:29]([S:30]([C:33]4[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=4[F:40])(=[O:32])=[O:31])[CH2:41][O:42][CH3:43])[C:23]=3[F:44])[N:21]=2)[C:7]([CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]2)=[O:9])=[O:14])[CH2:5][CH2:6][CH2:1][CH2:2][CH2:3]1

Participants

5

Reactant 3

HCID 7413Cyclohexanecarboxylic acidHCID 65578Oxalyl chlorideHCID 86704198HCID 86704198, compound

Product 1

HCID 86704199HCID 86704199, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

50 mg (0.39 mmol) of cyclohexanecarboxylic acid were dissolved in 3 mL of dry DCM and 56 μL (0.39 mmol) of TEA were added to the mixture. A solution of 33 μL of oxalyl chloride in 2 mL of DCM was then added dropwise at r.t. After 3 h the solvent was removed under reduced pressure, toluene was added several times and re-evaporated again. The residue was dissolved in 2 mL of dry DCM and dropped into a solution of 50 mg (0.095 mmol) of N-{3-[2-amino-5-(pyridin-4-yl)-1,3-thiazol-4-yl]-2,4-difluorophenyl}-2,5-difluoro-N-(methoxymethyl)benzenesulfonamide in 3 mL of the same solvent containing 56 μL of TEA. The reaction was maintained at r.t. overnight under stirring. The solution was then diluted with DCM and washed with aqueous NaHCO3. The organic layer was dried over Na2SO4 and evaporated, to give N-(cyclohexylcarbonyl)-N-[4-(3-{[(2,5-difluorophenyl)sulfonyl]-(methoxymethyl)amino}-2,6-difluorophenyl)-5-(pyridin-4-yl)-1,3-thiazol-2-yl]cyclohexanecarboxamide as an oil. The latter was taken up with 5 mL of MeOH and 1 mL of TEA was added to the resulting solution. The reaction was maintained at r. t. overnight. The solvent was then evaporated, the residue re-dissolved with DCM and washed with brine. The organic phase was dried over Na2SO4 and evaporated again, to afford N-[4-(3-{[(2,5-difluorophenyl)sulfonyl](methoxymethyl)-amino}-2,6-difluorophenyl)-5-(pyridin-4-yl)-1,3-thiazol-2-yl]cyclohexanecarboxamide. The latter was finally dissolved with 9 mL of TFA and 1 mL of water and heated at 75° C. for 6 h. The solvent was removed under reduced pressure, the residue re-dissolved with DCM and washed with aqueous NaHCO3. The organic layer was dried over Na2SO4 and evaporated. The crude was finally purified by flash chromatography on a silica gel precoated column, eluted with DCM-MeOH 98/2, yielding 35 mg (63% overall) of the title compound.

Workup

  1. customAfter 3 h the solvent was removed under reduced pressure, toluene
  2. additionwas added several times
  3. customre-evaporated again
  4. dissolutionThe residue was dissolved in 2 mL of dry DCM
  5. washwashed with aqueous NaHCO3
  6. dry with materialThe organic layer was dried over Na2SO4
  7. customevaporated

Sources & evidence

ORD record
ord-04314b04c878476d8a0faf086cb3b686
Source dataset
uspto-grants-2015_12
Patent number
US09199979B2

Reaction notes

Loading…