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 661057노트

반응식

HRID 661057 반응식
[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

참가 물질

4

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

(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).

후처리

  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)

출처 및 근거

ORD 기록
ord-9483192d069849c9996ec288b961b89f
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08084479B2

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