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 2109730Notes

Reaction equation

HRID 2109730 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-2a189cb2613647cc896569ff355fafca
Source dataset
uspto-grants-2009_04
Patent number
US07514566B2

Reaction notes

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