Ethanol → 8-[2-(Methylamino)-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one

HRID 1501850Notes

Reaction equation

HRID 1501850 reaction equation
[CH3:1][C:2]1[C:10]([C:11](=O)[CH2:12][N:13]2[CH2:30][CH2:29][C:16]3([C:20](=[O:21])[N:19]([C:22]4[CH2:23][O:24][C:25](=[O:28])[C:26]=4[CH3:27])[CH2:18][CH2:17]3)[CH2:15][CH2:14]2)=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][O:5][C:6]2=[O:32].[CH3:33][NH2:34].CCO.[BH4-].[Na+]>C1COCC1>[CH3:33][NH:34][CH:11]([C:10]1[CH:9]=[CH:8][C:7]2[C:6](=[O:32])[O:5][CH2:4][C:3]=2[C:2]=1[CH3:1])[CH2:12][N:13]1[CH2:14][CH2:15][C:16]2([C:20](=[O:21])[N:19]([C:22]3[CH2:23][O:24][C:25](=[O:28])[C:26]=3[CH3:27])[CH2:18][CH2:17]2)[CH2:29][CH2:30]1

Participants

6

Reactant 4

HCID 702EthanolHCID 6329MethylamineHCID 4311764Sodium borohydrideHCID 867095278-(2-(4-Methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)-2-oxoethyl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one

Product 1

HCID 729486488-[2-(Methylamino)-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 8-(2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)-2-oxoethyl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one (25 mg, 0.057 mmol) and methyl amine (4 mg, 0.114 mmol) in anhydrous THF was added Ti(O-iPr)4(35 μL, 0.114 mmol). The reaction was sealed and shaken at ambient temperature for 16 hr. To this reaction, EtOH (200 proof, 0.5 mL) was added followed by adding NaBH4 (11 mg, 0.171 mmol) portion-wise within 30 min. The reaction was shaken for 3 hr and quenched with water (0.5 mL). The reaction was partitioned between EtOAc (4 mL×2) and ammonium (2N, 1.5 mL). The organic phase was combined and evaporated under reduced pressure. The residue was dissolved in DMSO (1.5 mL) and filtered. The crude product was purified by using reversed-phase HPLC (Acetonitrile with 0.1% TFA: water with 0.1% TFA from 10% to 60%) to give the title compound. LC-MS (IE, m/z): 454 [M+1]+.

Workup

  1. customThe reaction was sealed
  2. additionwas added
  3. stirringThe reaction was shaken for 3 hr
  4. customquenched with water (0.5 mL)
  5. customThe reaction was partitioned between EtOAc (4 mL×2) and ammonium (2N, 1.5 mL)
  6. customevaporated under reduced pressure
  7. dissolutionThe residue was dissolved in DMSO (1.5 mL)
  8. filtrationfiltered
  9. customThe crude product was purified

Sources & evidence

ORD record
ord-b5fdbdf1d688417da4d3872de03d0830
Source dataset
uspto-grants-2015_12
Patent number
US09206198B2

Reaction notes

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