Methanol → 6-tert-Butyl-2-(2-hydroxymethyl-3-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-phenyl)-3,4-dihydro-2H-isoquinolin-1-one

HRID 2245697Notes

Reaction equation

HRID 2245697 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[C:11](=[O:15])[N:10]([C:16]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]3[CH:32]=[C:31]([NH:33][C:34]4[CH:39]=[CH:38][C:37]([C:40]([N:42]5[CH2:47][CH2:46][O:45][CH2:44][CH2:43]5)=[O:41])=[CH:36][N:35]=4)[C:30](=[O:48])[N:29]([CH3:49])[CH:28]=3)[C:17]=1[CH2:18][O:19]C(=O)C)[CH2:9][CH2:8]2)([CH3:4])([CH3:3])[CH3:2].CO.O.O.[OH-].[Li+]>C1COCC1>[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[C:11](=[O:15])[N:10]([C:16]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]3[CH:32]=[C:31]([NH:33][C:34]4[CH:39]=[CH:38][C:37]([C:40]([N:42]5[CH2:43][CH2:44][O:45][CH2:46][CH2:47]5)=[O:41])=[CH:36][N:35]=4)[C:30](=[O:48])[N:29]([CH3:49])[CH:28]=3)[C:17]=1[CH2:18][OH:19])[CH2:9][CH2:8]2)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 887Methanol2×HCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 59216446Acetic Acid 2-(6-tert-butyl-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl)-6-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-benzyl Ester

Product 1

HCID 445467746-tert-Butyl-2-(2-hydroxymethyl-3-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-phenyl)-3,4-dihydro-2H-isoquinolin-1-oneYield 33.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Acetic acid 2-(6-tert-butyl-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl)-6-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-benzyl ester (0.472 mmol) was taken up in THF (7 mL) and methanol (3 mL) and water (5 mL) and then added lithium hydroxide monohydrate (40 mg, 2 eq). The resulting mixture was stirred at room temperature overnight. The next morning the reaction was complete by TLC and most of the THF and methanol was removed under reduced pressure at 55° C. Then ethyl acetate (75 mL) and water (30 mL) were added and the layers were partitioned and then separated. Next, the ethyl acetate layer was washed with water (2×30 mL), brine (1×30 mL) and then dried over magnesium sulfate, filtered and concentrated to give 286 mg of crude product. Preparative Thin Layer Chromatography purification eluting on two 20×40 cm 1000 μM plates in 6% methanol in dicholomethane afforded the title compound (99 mg) as a white powder ((M+H)+=622).

Workup

  1. customwas removed under reduced pressure at 55° C
  2. additionThen ethyl acetate (75 mL) and water (30 mL) were added
  3. customthe layers were partitioned
  4. customseparated
  5. washNext, the ethyl acetate layer was washed with water (2×30 mL), brine (1×30 mL)
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give 286 mg of crude product
  10. customPreparative Thin Layer Chromatography purification
  11. washeluting on two 20×40 cm 1000 μM plates in 6% methanol in dicholomethane

Sources & evidence

ORD record
ord-7b3b9fd941e14af7b5dc701a0b8a9d33
Source dataset
uspto-grants-2010_03
Patent number
US07683064B2

Reaction notes

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