Trifluoroacetic acid → 4-(2-((S)-2-amino-3-(4-(trifluoromethyl)phenyl)propylamino)-5-(isoquinolin-6-yl)thiazol-4-yl)-2-methylbut-3-yn-2-ol

HRID 661057Notes

Reaction equation

HRID 661057 reaction equation
[OH:1][C:2]([CH3:50])([CH3:49])[C:3]#[C:4][C:5]1[N:6]=[C:7]([N:20](C(OC(C)(C)C)=O)[CH2:21][C@@H:22]([NH:34]C(=O)OC(C)(C)C)[CH2:23][C:24]2[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][CH:25]=2)[S:8][C:9]=1[C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][CH:19]=1)[CH:16]=[N:15][CH:14]=[CH:13]2.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:34][C@@H:22]([CH2:23][C:24]1[CH:25]=[CH:26][C:27]([C:30]([F:31])([F:33])[F:32])=[CH:28][CH:29]=1)[CH2:21][NH:20][C:7]1[S:8][C:9]([C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[CH:16]=[N:15][CH:14]=[CH:13]3)=[C:5]([C:4]#[C:3][C:2]([CH3:49])([OH:1])[CH3:50])[N:6]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 57634058(S)-tert-butyl 1-(N-(4-(3-hydroxy-3-methylbut-1-ynyl)-5-(isoquinolin-6-yl)thiazol-2-yl)-tert-butoxylcarbonylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate

Product 1

HCID 236546744-(2-((S)-2-amino-3-(4-(trifluoromethyl)phenyl)propylamino)-5-(isoquinolin-6-yl)thiazol-4-yl)-2-methylbut-3-yn-2-olYield 39.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(S)-tert-butyl 1-(N-(4-(3-hydroxy-3-methylbut-1-ynyl)-5-(isoquinolin-6-yl)thiazol-2-yl)-tert-butoxylcarbonylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate (0.010 g, 0.01 mmol) was taken up in 1 mL of DCM and TFA (0.2 mL) was added. After 1.5 hours, the solvent was removed under reduced pressure. The residue was loaded onto a Varian Mega Bond ELUT SCX column in MeOH, and eluted with 1M NH3 in MeOH to provide the free base. The solvent was removed under reduced pressure, and the residue was purified by flash chromatography on silica gel (pipette column, 2.5% to 10% MeOH/DCM) to afford 4-(2-((S)-2-amino-3-(4-(trifluoromethyl)phenyl)propylamino)-5-(isoquinolin-6-yl)thiazol-4-yl)-2-methylbut-3-yn-2-ol (0.002 g, 28% yield) as a yellow oil: LCMS (M+H) 511 calc. for C27H26F3N4OS 510.6. 1H NMR (400 MHz, CD3OD) δ ppm 9.17 (s, 1H) 8.41 (d, J=5.87 Hz, 1H) 8.28 (s, 1H) 8.07-8.13 (m, 2H) 7.79 (d, J=5.87 Hz, 1H) 7.62 (d, J=8.02 Hz, 2H) 7.47 (d, J=8.02 Hz, 2H), 3.47-3.25 (m, 3H) 2.95 (d, J=4.89 Hz, 1H) 2.73 (dd, J=13.40, 7.34 Hz, 1H) 1.60 (s, 6H).

Workup

  1. customthe solvent was removed under reduced pressure
  2. washeluted with 1M NH3 in MeOH
  3. customto provide the free base
  4. customThe solvent was removed under reduced pressure
  5. customthe residue was purified by flash chromatography on silica gel (pipette column, 2.5% to 10% MeOH/DCM)

Sources & evidence

ORD record
ord-9483192d069849c9996ec288b961b89f
Source dataset
uspto-grants-2011_12
Patent number
US08084479B2

Reaction notes

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