Trifluoroacetic acid methylene chloride → HCID 72548438, compound

HRID 879174Notes

Reaction equation

HRID 879174 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](SCCOC)[C@@H:26]([CH3:43])[CH2:25]2)=[O:16])[CH:12]=[CH:11][C:10]=1[F:44].O[O:46][S:47]([O-:49])=O.[K+].[C:51](O)([C:53](F)(F)F)=[O:52].[CH2:58](Cl)Cl>C1COCC1.O.CCOC(C)=O>[NH2:30][C@H:28]1[C@@H:27]([S:47]([CH2:53][CH2:51][O:52][CH3:58])(=[O:49])=[O:46])[C@@H:26]([CH3:43])[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:44])=[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 90056213HCID 90056213, compound

Product 1

HCID 72548438HCID 72548438, compoundYield 76%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of tert-butyl (1R,2S,3S,5R)-5-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-2-(2-methoxyethylthio)-3-methylcyclohexylcarbamate (1.0 equiv.) in THF (0.04 M) in a 0° C. bath was added oxone (2.0 equiv.) as a solution in H2O. The solution was left stirring at rt for 5 hrs. 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,4S,5S)-3-amino-4-((2-methoxyethyl)sulfonyl)-5-methylcyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide in 76% yield. LC/MS (m/z)=563.3 (MH+), Rt=0.62 min. 1H NMR (400 MHz, <dmso>) δ ppm 10.52 (s, 1H), 8.53 (s, 1H), 8.50 (d, J=4.0, 1H), 8.35 (dd, J=8.0, 4.0, 1H), 8.20 (t, J=8.0, 1H), 7.80 (bs, 2H), 7.70 (quintet, J=8.0, 1H), 7.36 (t, J=8.0, 2H), 7.31 (d, J=4.0, 1H), 3.82-3.88 (m, 2H), 3.73-3.78 (m, 2H), 3.55-3.61 (m, 1H), 3.42-3.49 (m, 1H), 3.31 (s, 3H), 3.06-3.16 (m, 1H), 1.92-2.18 (m, 4H), 1.54-1.64 (m, 1H), 1.22 (d, J=4.0, 3H).

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-c9706caef4334a56b31cb7fcc468c0fc
Source dataset
uspto-grants-2015_03
Patent number
US08987457B2

Reaction notes

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