Trifluoroacetic acid → Trifluoroacetic acid

HRID 1518382Notes

Reaction equation

HRID 1518382 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][NH:11][C:12]2[N:17]=[CH:16][N:15]=[C:14]3[N:18]([C:21]4[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][CH:22]=4)[N:19]=[CH:20][C:13]=23)[CH2:4][CH2:3]1.[H-].[Na+].[S:30]1[C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=2[N:32]=[C:31]1[NH:39][C:40]([C:42]1[CH:43]=[CH:44][CH:45]=[C:46]2[C:51]=1[CH2:50][N:49]([C:52]1[S:53][C:54]([CH2:62][CH2:63][CH2:64]I)=[C:55]([C:57]([O:59]CC)=[O:58])[N:56]=1)[CH2:48][CH2:47]2)=[O:41].[OH-].[Na+].[C:68]([OH:74])([C:70]([F:73])([F:72])[F:71])=[O:69]>CN(C=O)C.O.CO>[S:30]1[C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=2[N:32]=[C:31]1[NH:39][C:40]([C:42]1[CH:43]=[CH:44][CH:45]=[C:46]2[C:51]=1[CH2:50][N:49]([C:52]1[S:53][C:54]([CH2:62][CH2:63][CH2:64][N:11]([C:12]3[N:17]=[CH:16][N:15]=[C:14]4[N:18]([C:21]5[CH:22]=[CH:23][C:24]([OH:27])=[CH:25][CH:26]=5)[N:19]=[CH:20][C:13]=34)[CH2:10][CH2:9][CH2:8][N:5]3[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]3)=[C:55]([C:57]([OH:59])=[O:58])[N:56]=1)[CH2:48][CH2:47]2)=[O:41].[C:68]([OH:74])([C:70]([F:73])([F:72])[F:71])=[O:69]

Participants

10

Reactant 5

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 594474634-(4-(3-(4-methylpiperazin-1-yl)propylamino)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)phenolHCID 59447467ethyl 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-iodopropyl)thiazole-4-carboxylate

Product 2

HCID 6422Trifluoroacetic acidHCID 468368642-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-((1-(4-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)(3-(4-methylpiperazin-1-yl)propyl)amino)propyl)thiazole-4-carboxylic acid

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution compound 84A (50 mg, 0.136 mmol) in DMF (5 ml) was added sodium hydride (27.2 mg, 0.680 mmol)(60%). The reaction mixture was stirred for 10 min and compound 2C (77 mg, 0.122 mmol) was added. The resulting mixture was stirred for 1 hour and methanol (3 ml), 10% NaOH and water (1 ml) were added. The mixture was stirred overnight, acidified with TFA and concentrated. The residue was dissolved in a mixture of DMSO-methanol and purified by reverse phase HPLC (mobile phase: 0%-60% acetonitrile in 0.1% TFA aqueous solution during 60 min) to provide the title compound 91 as a TFA salt: 1H NMR (500 MHz, PYRIDINE-D5) δ ppm 8.62 (1H, s), 8.41 (1H, s), 8.35 (2H, d), 7.94 (1H, d), 7.89 (1H, d), 7.77-7.81 (1H, m), 7.43 (1H, t), 7.24-7.33 (5H, m), 5.15 (2H, s), 3.93-4.01 (2H, m), 3.87 (2H, d), 3.81 (2H, t), 3.45 (2H, t), 2.92 (2H, t), 2.79-2.85 (4H, m), 2.62-2.69 (4H, m), 2.42-2.47 (5H, m), 2.18-2.28 (2H, m), 1.89-1.98 (2H, m); LCMS (APCI) m/e 844 (M+H).

Workup

  1. stirringThe resulting mixture was stirred for 1 hour
  2. stirringThe mixture was stirred overnight
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in a mixture of DMSO-methanol
  5. custompurified by reverse phase HPLC (mobile phase: 0%-60% acetonitrile in 0.1% TFA aqueous solution during 60 min)

Sources & evidence

ORD record
ord-9962f6c9fbc0432fade025819d121b86
Source dataset
uspto-grants-2012_07
Patent number
US08232273B2

Reaction notes

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