Sodium Hydroxide → HCID 67281240, compound

HRID 515501Notes

Reaction equation

HRID 515501 reaction equation
[CH3:1][N:2]1[C:7](=[O:8])[CH:6]=[C:5]([C:9]2[CH:14]=[CH:13][N:12]=[CH:11][N:10]=2)[N:4]=[C:3]1[N:15]1[CH2:21][CH2:20][CH2:19][O:18][C@@H:17]([C:22]2[CH:23]=[C:24]([CH:28]=[CH:29][CH:30]=2)[C:25]([NH2:27])=[O:26])[CH2:16]1.O1[CH2:36][CH2:35]OCC1.[OH-].[Na+].Cl.[NH2:40]O>COC(OC)(N(C)C)C.C(O)(=O)C>[CH3:1][N:2]1[C:7](=[O:8])[CH:6]=[C:5]([C:9]2[CH:14]=[CH:13][N:12]=[CH:11][N:10]=2)[N:4]=[C:3]1[N:15]1[CH2:21][CH2:20][CH2:19][O:18][C@@H:17]([C:22]2[CH:30]=[CH:29][CH:28]=[C:24]([C:25]3[O:26][N:40]=[C:35]([CH3:36])[N:27]=3)[CH:23]=2)[CH2:16]1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 312751,4-DioxaneHCID 443297Hydroxyamine hydrochlorideHCID 46936067HCID 46936067, compound

Product 1

HCID 67281240HCID 67281240, compoundYield 53%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 878351,1-Dimethoxyethyl(dimethyl)amineSolvent

Conditions

Temperature
100 °C

Procedure

A solution of (S)-3-[4-(1-Methyl-6-oxo-1,6-dihydro-[4,4′]bipyrimidinyl-2-yl)-[1,4]oxazepan-2-yl]-benzamide (A015) (200 mg, 0.492 mmol) in N,N-dimethylacetamide dimethyl acetal (0.760 ml) was stirred at 110° C. for one hour. The mixture was concentrated under reduced pressure, and then 1,4-dioxane (0.820 ml), acetic acid (0.820 ml), 1N-sodium hydroxide (0.490 ml) and hydroxylamine hydrochloride (43.1 mg 0.491 mmol) was added. The mixture was stirred at 100° C. for 3 hours and partitioned between water and chloroform. The organic layer was washed with brine and aqueous sodium hydrogen carbonate, dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluant; chloroform/methanol=98/2) to afford (S)-1-Methyl-2-{2-[3-(3-methyl-[1,2,4]oxadiazol-5-yl)-phenyl]-[1,4]oxazepan-4-yl}-1H-[4,4′]bipyrimidinyl-6-one (A045) as pale yellow solid (116 mg, 53%).

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. custompartitioned between water and chloroform
  3. washThe organic layer was washed with brine and aqueous sodium hydrogen carbonate
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (eluant; chloroform/methanol=98/2)

Sources & evidence

ORD record
ord-bb0767b04e1f4682be88c17c13577a42
Source dataset
uspto-grants-2015_08
Patent number
US09108957B2

Reaction notes

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