Trifluoroacetic acid → HCID 46836643, compound

HRID 1518272Notes

Reaction equation

HRID 1518272 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]([C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[CH2:21][N:20]([C:23]1[S:24][C:25]([CH2:31][CH2:32][CH2:33][O:34][C:35]3[CH:40]=[CH:39][C:38]([NH:41]C(OC(C)(C)C)=O)=[CH:37][CH:36]=3)=[C:26]([C:28]([OH:30])=[O:29])[N:27]=1)[CH2:19][CH2:18]2)=[O:12].C(O)(C(F)(F)F)=O>CO>[NH2:41][C:38]1[CH:37]=[CH:36][C:35]([O:34][CH2:33][CH2:32][CH2:31][C:25]2[S:24][C:23]([N:20]3[CH2:19][CH2:18][C:17]4[C:22](=[C:13]([C:11](=[O:12])[NH:10][C:2]5[S:1][C:5]6[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=6[N:3]=5)[CH:14]=[CH:15][CH:16]=4)[CH2:21]3)=[N:27][C:26]=2[C:28]([OH:30])=[O:29])=[CH:40][CH:39]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 46836570HCID 46836570, compound

Product 1

HCID 46836643HCID 46836643, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The title compound 5-(3-(4-aminophenoxy)propyl)-2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)thiazole-4-carboxylic acid (6) was prepared by the following procedure: To 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-(4-(tert-butoxycarbonylamino)phenoxy)propyl)thiazole-4-carboxylic acid (4) (20 mg, 0.029 mmol) in MeOH (1 mL) was added TFA (1 mL, 13 mmol) and stirred at rt for 2 hours. The reaction mixture was purified by HPLC (Preparative reverse phase HPLC was performed on an automated Gilson HPLC system, using a SymmetryPrep Shield RP18 prep cartridge, 250 mm×21.20 mm i.d., 10 um, and a flow rate of 25 mL/min; λ=214, 245 nm; mobile phase A, 0.1% TFA in H2O; mobile phase B, CH3CN; linear gradient 0-70% of B in 40 minutes) to provide the desired product 5-(3-(4-aminophenoxy)propyl)-2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)thiazole-4-carboxylic acid in 48% yield. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.77 (1H, s), 9.04 (1H, s), 8.03 (1H, d), 7.79 (1H, d), 7.67 (1H, d), 7.47 (2H, m), 7.37 (2H, m), 7.09 (2H, d), 6.92 (2H, m), 4.83 (2H, s), 3.95 (2H, t), 3.72 (2H, t), 3.17 (2H, m), 3.03 (2H, t), 1.99 (2H, m). MS (ESI(+)): m/z 586 (M+H).

Workup

  1. customThe title compound 5-(3-(4-aminophenoxy)propyl)-2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)thiazole-4-carboxylic acid (6) was prepared by the following procedure
  2. customThe reaction mixture was purified by HPLC (Preparative reverse phase HPLC

Sources & evidence

ORD record
ord-c50cad303b0343bfb2c96f70f3c0e355
Source dataset
uspto-grants-2012_07
Patent number
US08232273B2

Reaction notes

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