Cyclopropylamine → 8-(2-(Cyclopropylamino)-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one

HRID 1848539Notes

Reaction equation

HRID 1848539 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].[CH:33]1([NH2:36])[CH2:35][CH2:34]1.[BH3-]C#N.[Na+]>CC(O)=O.C1COCC1>[CH:33]1([NH:36][CH:11]([C:10]2[C:2]([CH3:1])=[C:3]3[C:7](=[CH:8][CH:9]=2)[C:6](=[O:32])[O:5][CH2:4]3)[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)[CH2:35][CH2:34]1

Participants

5

Reactant 3

HCID 69828CyclopropylamineHCID 5003444Sodium cyanoborohydrideHCID 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 729484658-(2-(Cyclopropylamino)-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-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 23444217Acetic acid tetrahydrofuranSolvent

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 cyclopropanamine (6.5 mg, 0.114 mmol) in anhydrous 5% HOAc/THF (1 mL) was added NaCNBH3 (18 mg, 0.28 mmol). The reaction was sealed and shaken at ambient temperature for 16 h. LCMS showed that the product was formed. The reaction was quenched with water (0.5 mL) and the solvent was 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): 480 [M+1]+.

Workup

  1. customThe reaction was sealed
  2. customwas formed
  3. customThe reaction was quenched with water (0.5 mL)
  4. customthe solvent was evaporated under reduced pressure
  5. dissolutionThe residue was dissolved in DMSO (1.5 mL)
  6. filtrationfiltered
  7. customThe crude product was purified

Sources & evidence

ORD record
ord-53e906b0b5314759b1a4bf3842f916c9
Source dataset
uspto-grants-2015_02
Patent number
US08952166B2

Reaction notes

Loading…