Trifluoroacetic acid → 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-(4-(4-(3-(dimethylamino)propylamino)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)phenoxy)propyl)thiazole-4-carboxylic acid

HRID 1518334Notes

Reaction equation

HRID 1518334 reaction equation
[CH3:1][N:2]([CH3:23])[CH2:3][CH2:4][CH2:5][NH:6][C:7]1[N:12]=[CH:11][N:10]=[C:9]2[N:13]([C:16]3[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=3)[N:14]=[CH:15][C:8]=12.[H-].[Na+].[S:26]1[C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=2[N:28]=[C:27]1[NH:35][C:36]([C:38]1[CH:39]=[CH:40][CH:41]=[C:42]2[C:47]=1[CH2:46][N:45]([C:48]1[S:49][C:50]([CH2:58][CH2:59][CH2:60]I)=[C:51]([C:53]([O:55]CC)=[O:54])[N:52]=1)[CH2:44][CH2:43]2)=[O:37].[OH-].[Na+].C(O)(C(F)(F)F)=O>CN(C=O)C.O.CO>[S:26]1[C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=2[N:28]=[C:27]1[NH:35][C:36]([C:38]1[CH:39]=[CH:40][CH:41]=[C:42]2[C:47]=1[CH2:46][N:45]([C:48]1[S:49][C:50]([CH2:58][CH2:59][CH2:60][O:22][C:19]3[CH:18]=[CH:17][C:16]([N:13]4[C:9]5=[N:10][CH:11]=[N:12][C:7]([NH:6][CH2:5][CH2:4][CH2:3][N:2]([CH3:1])[CH3:23])=[C:8]5[CH:15]=[N:14]4)=[CH:21][CH:20]=3)=[C:51]([C:53]([OH:55])=[O:54])[N:52]=1)[CH2:44][CH2:43]2)=[O:37]

Participants

9

Reactant 5

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 59447467ethyl 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-iodopropyl)thiazole-4-carboxylateHCID 594476574-(4-(3-(dimethylamino)propylamino)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)phenol

Product 1

HCID 468363052-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-(4-(4-(3-(dimethylamino)propylamino)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)phenoxy)propyl)thiazole-4-carboxylic acid

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of compound 54A (160 mg, 0.512 mmol) in DMF (5 ml) was added sodium hydride (102 mg, 2.56 mmol)(60%). The reaction mixture was stirred for 10 min and Example 2C (194 mg, 0.307 mmol) was added. The resulting mixture was stirred for 1 hour and methanol (3 ml), 10% NaOH (3 ml) and water (1 ml) were added. The resulting 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%-55% acetonitrile in 0.1% TFA aqueous solution during 60 min) to provide the title compound: 1H NMR (400 MHz, DMSO-D6) δ ppm 12.84 (1H, s), 9.34 (1H, s), 8.53 (1H, t), 8.36 (1H, s), 8.32 (1H, s), 7.96-8.03 (3H, m), 7.78 (1H, d), 7.67 (1H, d), 7.42-7.49 (2H, m), 7.32-7.41 (2H, m), 7.05-7.10 (2H, m), 4.84 (2H, s), 4.04 (2H, t), 3.73 (2H, t), 3.60 (2H, q), 3.12-3.26 (4H, m), 3.03 (2H, t), 2.80 (6H, s), 1.93-2.08 (4H, m). LCMS (APCI) m/e 789 (M+H).

Workup

  1. stirringThe resulting mixture was stirred for 1 hour
  2. stirringThe resulting 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%-55% acetonitrile in 0.1% TFA aqueous solution during 60 min)

Sources & evidence

ORD record
ord-0540b537b432452aa85fd9d28b183838
Source dataset
uspto-grants-2012_07
Patent number
US08232273B2

Reaction notes

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