Trifluoroacetic acid methylene chloride → HCID 90056215, compound

HRID 705263Notes

Reaction equation

HRID 705263 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[N:14]=[C:13]([C:15]([NH:17][C:18]2[CH:19]=[N:20][CH:21]=[CH:22][C:23]=2[C@H:24]2[CH2:29][C@@H:28]([NH:30]C(=O)OC(C)(C)C)[C@H:27]([S:38][CH3:39])[C@@H:26]([CH3:40])[CH2:25]2)=[O:16])[CH:12]=[CH:11][C:10]=1[F:41].[OH:42]OS([O-])=O.[K+].C(O)(C(F)(F)F)=O.C(Cl)Cl>C1COCC1.O.CCOC(C)=O>[NH2:30][C@H:28]1[C@H:27]([S@:38]([CH3:39])=[O:42])[C@@H:26]([CH3:40])[CH2:25][C@@H:24]([C:23]2[CH:22]=[CH:21][N:20]=[CH:19][C:18]=2[NH:17][C:15](=[O:16])[C:13]2[CH:12]=[CH:11][C:10]([F:41])=[C:9]([C:3]3[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=3[F:8])[N:14]=2)[CH2:29]1

Participants

7

Reactant 3

HCID 21863450Trifluoroacetic acid methylene chlorideHCID 23707502Potassium hydroxy sulfiteHCID 86705221HCID 86705221, compound

Product 1

HCID 90056215HCID 90056215, compoundYield 33%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of tert-butyl (1R,2R,3S,5R)-5-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-3-methyl-2-(methylthio)cyclohexylcarbamate (1.0 equiv.) in THF (0.05 M) in a 0° C. bath was added the oxone (1.0 equiv.) as a solution in H2O. The solution was left stirring at 0° C. for 5 mins. The solution was diluted with EtOAc, washed with H2O, NaCl(sat), dried over MgSO4, filtered, concentrated to yield Boc protected product. The material was treated with 25% TFA/CH2Cl2 for 30 minutes, at which time the volatiles were removed in vacuo, the residue was dissolved in DMSO and purified by reverse phase HPLC. The product fractions were lyophilized directly to yield N-(4-((1R,3R,4R,5S)-3-amino-5-methyl-4-((S)-methylsulfinyl)cyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide in 33% yield, LC/MS=503.2 (MH+), Rt=0.58 min; and N-(4-((1R,3R,4R,5S)-3-amino-5-methyl-4-((R)-methylsulfinyl)cyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide in 37% yield. LC/MS (m/z)=503.2 (MH+), Rt=0.60 min.

Workup

  1. waitThe solution was left
  2. washwashed with H2O, NaCl(sat)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto yield Boc protected product
  7. customwere removed in vacuo
  8. dissolutionthe residue was dissolved in DMSO
  9. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-1c74c11e05e94f488dfc52952e0fe459
Source dataset
uspto-grants-2015_11
Patent number
US09173883B2

Reaction notes

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