Lithium hydroxide, monohydrate → (R)-2-[2-(1-Hydroxy-ethyl)-pyrimidin-4-yl]-1,2,3,4-tetrahydro-isoquinoline-7-sulfonic acid dimethylamide

HRID 394533Notes

Reaction equation

HRID 394533 reaction equation
C([O:4][C@@H:5]([C:7]1[N:12]=[C:11]([N:13]2[CH2:22][CH2:21][C:20]3[C:15](=[CH:16][C:17]([S:23](=[O:28])(=[O:27])[N:24]([CH3:26])[CH3:25])=[CH:18][CH:19]=3)[CH2:14]2)[CH:10]=[CH:9][N:8]=1)[CH3:6])(=O)C.O.[OH-].[Li+]>CO.O>[CH3:26][N:24]([CH3:25])[S:23]([C:17]1[CH:16]=[C:15]2[C:20]([CH2:21][CH2:22][N:13]([C:11]3[CH:10]=[CH:9][N:8]=[C:7]([C@H:5]([OH:4])[CH3:6])[N:12]=3)[CH2:14]2)=[CH:19][CH:18]=1)(=[O:28])=[O:27]

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 69735145(R)-1-[4-(7-Dimethylsulfamoyl-3,4-dihydro-1H-isoquinoline-2-yl)-pyrimidin-2-yl]-ethyl acetate

Product 1

HCID 57157881(R)-2-[2-(1-Hydroxy-ethyl)-pyrimidin-4-yl]-1,2,3,4-tetrahydro-isoquinoline-7-sulfonic acid dimethylamideYield 31%

Reagents, catalysts & solvents 1

HCID 22242641Methanol--water (1/1)Solvent

Procedure

To a solution of (R)-1-[4-(7-dimethylsulfamoyl-3,4-dihydro-1H-isoquinolin-2-yl)-pyrimidin-2-yl]-ethyl acetate (prepared according to the method of Example 247, Step C, 326 mg, 0.81 mmol) in a 4:1 mixture of methanol/water (8 mL) was added lithium hydroxide hydrate (170 mg, 4.0 mmol). This mixture was stirred at room temperature for 50 min, concentrated, re-suspended in water, and extracted with 10% isopropanol/chloroform (3×). The combined organic extracts were dried over sodium sulfate, filtered, evaporated, and purified by flash column chromatography (1% methanol/chloroform) to give a white foam which was further purified by recrystallization from ether/methanol to give 90 mg (31%) of the title compound as a white solid. mp: 120.5-122° C.; 1H NMR (CDCl3, 300 MHz) δ 8.24 (d, 1H), 7.62-7.59 (c, 2H), 7.35 (d, 1H), 6.44 (d, 1H), 4.83 (s, 2H), 4.73 (q, 1H), 4.34 (br s, 1H), 3.93-3.85 (c, 2H), 3.03 (t, 2H), 2.71 (s, 6H), 1.52 (d, 3H); MS (TS) 363 (MH+).

Workup

  1. concentrationconcentrated
  2. extractionextracted with 10% isopropanol/chloroform (3×)
  3. dry with materialThe combined organic extracts were dried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. custompurified by flash column chromatography (1% methanol/chloroform)
  7. customto give a white foam which
  8. customwas further purified by recrystallization from ether/methanol

Sources & evidence

ORD record
ord-b28b0eee549c419cb653ecea66e045b0
Source dataset
uspto-grants-2003_08
Patent number
US06602875B2

Reaction notes

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