Sodium Hydroxide → 2-[8-(1,3-Benzothiazol-2-Ylcarbamoyl)-3,4-Dihydroisoquinolin-2(1h)-Yl]-5-{3-[4-(1h-Pyrazolo[3,4-D]pyrimidin-1-Yl)phenoxy]propyl}-1,3-Thiazole-4-Carboxylic Acid

HRID 1518283Notes

Reaction equation

HRID 1518283 reaction equation
[N:1]1([C:10]2[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=2)[C:5]2=[N:6][CH:7]=[N:8][CH:9]=[C:4]2[CH:3]=[N:2]1.[H-].[Na+].[S:19]1[C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=2[N:21]=[C:20]1[NH:28][C:29]([C:31]1[CH:32]=[CH:33][CH:34]=[C:35]2[C:40]=1[CH2:39][N:38]([C:41]1[S:42][C:43]([CH2:51][CH2:52][CH2:53]I)=[C:44]([C:46]([O:48]CC)=[O:47])[N:45]=1)[CH2:37][CH2:36]2)=[O:30].[OH-].[Na+]>CN(C=O)C.CO.C1COCC1>[N:1]1([C:10]2[CH:11]=[CH:12][C:13]([O:16][CH2:53][CH2:52][CH2:51][C:43]3[S:42][C:41]([N:38]4[CH2:37][CH2:36][C:35]5[C:40](=[C:31]([C:29](=[O:30])[NH:28][C:20]6[S:19][C:23]7[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=7[N:21]=6)[CH:32]=[CH:33][CH:34]=5)[CH2:39]4)=[N:45][C:44]=3[C:46]([OH:48])=[O:47])=[CH:14][CH:15]=2)[C:5]2=[N:6][CH:7]=[N:8][CH:9]=[C:4]2[CH:3]=[N:2]1

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 594187194-(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 1

HCID 468368622-[8-(1,3-Benzothiazol-2-Ylcarbamoyl)-3,4-Dihydroisoquinolin-2(1h)-Yl]-5-{3-[4-(1h-Pyrazolo[3,4-D]pyrimidin-1-Yl)phenoxy]propyl}-1,3-Thiazole-4-Carboxylic Acid

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of compound 21D (106 mg, 0.498 mmol) in DMF (5 mL) was added sodium hydride (56.9 mg, 1.423 mmol). The resulting mixture was stirred at rt for 30 minutes and compound 2C (300 mg, 0.474 mmol) was added. The reaction mixture was stirred for 1 hour and 10% sodium hydroxide (1.897 mL, 4.74 mmol), THF (5 mL) and MeOH (3 mL) was added. The resulting mixture was stirred at 70° C. overnight, cooled, and filtered. The filtrate was acidified by HCl to pH 4. The precipitate was collected and dried to provide the desired product: 1H NMR (400 MHz, DMSO-D6) δ ppm 12.85 (1H, s), 9.45 (1H, s), 9.10 (1H, s), 8.61 (1H, s), 7.98-8.06 (3H, m), 7.78 (1H, d), 7.67 (1H, d), 7.42-7.50 (2H, m), 7.32-7.40 (2H, m), 7.09-7.16 (2H, m), 4.84 (2H, s), 4.06 (2H, t), 3.73 (2H, t), 3.14-3.24 (2H, m), 3.03 (2H, t), 1.98-2.12 (2H, m); LCMS (APCI): m/z 687 (M+H).

Workup

  1. stirringThe reaction mixture was stirred for 1 hour
  2. stirringThe resulting mixture was stirred at 70° C. overnight
  3. temperaturecooled
  4. filtrationfiltered
  5. customThe precipitate was collected
  6. customdried

Sources & evidence

ORD record
ord-43972c3fd67a4c289d390319e516c3b6
Source dataset
uspto-grants-2012_07
Patent number
US08232273B2

Reaction notes

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