Trifluoroacetic acid methylene chloride → HCID 90055863, compound

HRID 705261Notes

Reaction equation

HRID 705261 reaction equation
[Si](OCCS[C@H:12]1[C@@H:17]([CH3:18])[CH2:16][C@@H:15]([C:19]2[CH:24]=[CH:23][N:22]=[CH:21][C:20]=2[NH:25][C:26](=[O:42])[C:27]2[CH:32]=[CH:31][C:30]([F:33])=[C:29]([C:34]3[C:39]([F:40])=[CH:38][CH:37]=[CH:36][C:35]=3[F:41])[N:28]=2)[CH2:14][C@H:13]1[NH:43]C(=O)OC(C)(C)C)(C(C)(C)C)(C)C.O[O:52][S:53]([O-:55])=O.[K+].[C:57](O)([C:59](F)(F)F)=[O:58].C(Cl)Cl>C1COCC1.O.CCOC(C)=O>[NH2:43][C@H:13]1[C@@H:12]([S:53]([CH2:59][CH2:57][OH:58])(=[O:55])=[O:52])[C@@H:17]([CH3:18])[CH2:16][C@@H:15]([C:19]2[CH:24]=[CH:23][N:22]=[CH:21][C:20]=2[NH:25][C:26](=[O:42])[C:27]2[CH:32]=[CH:31][C:30]([F:33])=[C:29]([C:34]3[C:35]([F:41])=[CH:36][CH:37]=[CH:38][C:39]=3[F:40])[N:28]=2)[CH2:14]1

Participants

7

Reactant 3

HCID 21863450Trifluoroacetic acid methylene chlorideHCID 23707502Potassium hydroxy sulfiteHCID 131732629HCID 131732629, compound

Product 1

HCID 90055863HCID 90055863, compoundYield 44%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of tert-butyl (1R,2S,3S,5R)-2-(2-(tert-butyldimethylsilyloxy)ethylthio)-5-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-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 48 hrs. The solution was diluted with EtOAc, washed with H2O, Na2CO3(sat), 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 N-(4-((1R,3R,4S,5S)-3-amino-4-(2-hydroxyethylsulfonyl)-5-methylcyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide in 44% yield. LC/MS (m/z)=549.6 (MH+), Rt=0.58 min. 1H NMR (400 MHz, <dmso>) δ ppm 10.51 (s, 1H), 8.53 (s, 1H), 8.51 (d, J=4.0, 1H), 8.33 (dd, J=8.0, 4.0, 1H), 8.20 (t, J=8.0, 1H), 8.09 (broad doublet, J=4.0, 2H), 7.65-7.75 (m, 1H), 7.36 (t, J=8.0, 2H), 7.30 (d, J=8.0, 1H), 3.84-4.02 (m, 3H), 3.58-3.68 (m, 1H), 3.43-3.53 (m, 1H), 3.28-3.36 (m, 1H), 3.04-3.14 (m, 1H), 1.92-2.18 (m, 4 H), 1.56-1.63 (m, 1H), 1.24 (d, J=8.0, 3H).

Workup

  1. waitThe solution was left
  2. washwashed with H2O, Na2CO3(sat), 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-6257aa36fac743789b4becbf3e2c77a9
Source dataset
uspto-grants-2015_11
Patent number
US09173883B2

Reaction notes

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