Methanol → HCID 58550127, compound

HRID 2068895Notes

Reaction equation

HRID 2068895 reaction equation
C([O:8][CH2:9][C:10]1([CH3:56])[CH2:18][C:17]2[N:16]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[N:15]=[C:14]([C:27]3[N:28]([CH2:48][O:49][CH2:50][CH2:51][Si:52]([CH3:55])([CH3:54])[CH3:53])[C:29]4[C:34]([CH:35]=3)=[CH:33][CH:32]=[C:31]([N:36]([CH3:47])[C:37](=[O:46])[CH2:38][N:39]3[CH2:44][CH2:43][CH2:42][CH2:41][C:40]3=[O:45])[CH:30]=4)[C:13]=2[CH2:12][CH2:11]1)C1C=CC=CC=1.CO>[OH-].[Pd+2].[OH-].[C].O1CCCC1>[OH:8][CH2:9][C:10]1([CH3:56])[CH2:18][C:17]2[N:16]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:24])([CH3:26])[CH3:25])[N:15]=[C:14]([C:27]3[N:28]([CH2:48][O:49][CH2:50][CH2:51][Si:52]([CH3:53])([CH3:55])[CH3:54])[C:29]4[C:34]([CH:35]=3)=[CH:33][CH:32]=[C:31]([N:36]([CH3:47])[C:37](=[O:46])[CH2:38][N:39]3[CH2:44][CH2:43][CH2:42][CH2:41][C:40]3=[O:45])[CH:30]=4)[C:13]=2[CH2:12][CH2:11]1

Participants

5

Reactant 2

HCID 887MethanolHCID 58550372HCID 58550372, compound

Product 1

HCID 58550127HCID 58550127, compoundYield 85.6%

Reagents, catalysts & solvents 2

HCID 178502593HCID 178502593, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-(2-{6-benzyloxymethyl-6-methyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indol-6-yl)-N-methylamine (150 mg, 0.23 mmol) in N,N-dimethylformamide (3 ml) were added (2-oxopiperidin-1-yl)acetic acid obtained in Reference Example 6 (43 mg, 0.27 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (52 mg, 0.27% mmol) and 1-hydroxybenzotriazole monohydrate (37 mg, 0.27 mmol), and the mixture was stirred at room temperature overnight. To the reaction mixture were added ethyl acetate and water, and the organic layer was separated, washed successively with water and saturated brine, and dried over sodium sulfate. Sodium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography to give N-(2-{6-benzyloxymethyl-6-methyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indol-6-yl)-N-methyl-2-(2-oxopiperidin-1-yl)acetamide (158 mg). Under a nitrogen atmosphere, to a solution of the obtained N-(2-{6-benzyloxymethyl-6-methyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indol-6-yl)-N-methyl-2-(2-oxopiperidin-1-yl)acetamide (158 mg) in a mixed solvent of methanol (0.8 ml) and tetrahydrofuran (0.8 ml) was added 20% palladium hydroxide-carbon (150 mg) at room temperature, and the mixture was stirred under a hydrogen atmosphere at normal pressure for 4 hr. The reaction mixture was filtered through celite, and the filtrate was concentrated under reduced pressure to give the title compound (120 mg, yield 75%).

Workup

  1. filtrationThe reaction mixture was filtered through celite
  2. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-40316934835640ff82d8f1369772d084
Source dataset
uspto-grants-2012_10
Patent number
US08299070B2

Reaction notes

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