Trifluoroacetic acid → HCID 72547731, compound

HRID 879173Notes

Reaction equation

HRID 879173 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]([CH3:41])(=[O:40])=[O:39])[C@@H:26]([CH3:42])[CH2:25]2)=[O:16])[CH:12]=[CH:11][C:10]=1[F:43].C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:30][C@H:28]1[C@@H:27]([S:38]([CH3:41])(=[O:40])=[O:39])[C@@H:26]([CH3:42])[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:43])=[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

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86705220HCID 86705220, compound

Product 1

HCID 72547731HCID 72547731, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl (1R,2S,3S,5R)-5-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-3-methyl-2-(methylsulfonyl)cyclohexylcarbamate in DCM (0.02 M) was added TFA (30.0 equiv.). The solution was capped and left standing at rt for 1 hr. 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-5-methyl-4-(methylsulfonyl)cyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide in 73% yield. LC/MS (m/z)=519.2 (MH+), Rt=0.58 min. 1H NMR (400 MHz, <dmso>) δ ppm 10.52 (s, 1H), 8.51-8.54 (m, 2H), 8.34 (dd, J=8.0, 4.0, 1H), 8.20 (dd, J=8.0, 8.0, 1H), 8.15 (dd, J=16.0, 4.0, 1H), 7.67-7.74 (m, 1H), 7.36 (dd, J=8.0, 8.0, 2H), 7.28 (d, J=4.0, 1H), 3.77-3.79 (m, 1H), 3.18 (s, 3H), 3.02-3.20 (m, 1H), 1.94-2.40 (m, 5H), 1.57-1.62 (m, 1H), 1.24 (d, J=8.0, 3H).

Workup

  1. customThe solution was capped
  2. waitleft
  3. customThe volatiles were removed in vacuo
  4. dissolutionthe residue was dissolved in DMSO
  5. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-eff439c9b2f84628a4f66380d407ec3a
Source dataset
uspto-grants-2015_03
Patent number
US08987457B2

Reaction notes

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