Trifluoroacetic acid → 5-(2-((S)-2-amino-3-(4-(trifluoromethyl)phenyl)propylamino)thiazol-5-yl)-2-fluorobenzonitrile

HRID 2109714Notes

Reaction equation

HRID 2109714 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:10]2[S:14][C:13]([NH:15][CH2:16][C@@H:17]([NH:29]C(=O)OC(C)(C)C)[CH2:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=3)=[N:12][CH:11]=2)[CH:6]=[CH:7][C:8]=1[F:9])#[N:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:29][C@@H:17]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]([F:26])([F:28])[F:27])=[CH:21][CH:20]=1)[CH2:16][NH:15][C:13]1[S:14][C:10]([C:5]2[CH:6]=[CH:7][C:8]([F:9])=[C:3]([CH:4]=2)[C:1]#[N:2])=[CH:11][N:12]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 86613766tert-butyl (S)-1-(5-(3-cyano-4-fluorophenyl)thiazol-2-ylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate

Product 1

HCID 866137675-(2-((S)-2-amino-3-(4-(trifluoromethyl)phenyl)propylamino)thiazol-5-yl)-2-fluorobenzonitrileYield 96%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl (S)-1-(5-(3-cyano-4-fluorophenyl)thiazol-2-ylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate (0.18 g, 0.35 mmol) in 7 mL of DCM was added TFA (0.40 mL, 5.2 mmol). After 30 minutes, 2 mL of additional TFA was added. The mixture was stirred for 30 minutes and was then concentrated under reduced pressure. The residue was taken up in 30 mL of 1:1 EtOAc to 2 N aqueous Na2CO3. The mixture was partitioned in a separatory funnel, and the aqueous portion was extracted with 25 mL of EtOAc. The combined organic extracts were washed with brine and dried over MgSO4. Filtration and concentration under reduced pressure, followed by flash chromatography on silica gel (2.5% to 10% MeOH/DCM) afforded 5-(2-((S)-2-amino-3-(4-(trifluoromethyl)phenyl)propylamino)thiazol-5-yl)-2-fluorobenzonitrile (0.14 g, 0.33 mmol, 96% yield) as a yellow solid. 1H NMR (400 MHz, CD3OD) δ ppm 7.83 (dd, J=5.8, 2.4 Hz, 1H), 7.76 (ddd, J=8.7, 5.0, 2.4 Hz, 1H), 7.68 (d, J=8.2 Hz, 2H), 7.52 (d, J=7.8 Hz, 2H), 7.48 (s, 1H), 7.35 (t, J=9.0 Hz, 1H), 3.84-3.78 (m, 1H), 3.68-3.63 (m, 1H), 3.55-3.47 (m, 1H), 3.14-3.04 (m, 2H) LCMS (M+H) 421 calc. for C20H19F3N4OS 420.43.

Workup

  1. concentrationwas then concentrated under reduced pressure
  2. customThe mixture was partitioned in a separatory funnel
  3. extractionthe aqueous portion was extracted with 25 mL of EtOAc
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationFiltration and concentration under reduced pressure

Sources & evidence

ORD record
ord-ed5b5604ca014688967be915648ae71d
Source dataset
uspto-grants-2009_04
Patent number
US07514566B2

Reaction notes

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