N,N-Dimethylglycine → 2-(3-{2-[1-(N,N-Dimethylglycyl)piperidin-4-yl]-1,3-thiazol-4-yl}-4,5-dihydro-1,2-oxazol-5-yl)phenyl methanesulphonate

HRID 2206874Notes

Reaction equation

HRID 2206874 reaction equation
[Cl-].[CH3:2][S:3]([O:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[CH:13]1[O:17][N:16]=[C:15]([C:18]2[N:19]=[C:20]([CH:23]3[CH2:28][CH2:27][NH2+:26][CH2:25][CH2:24]3)[S:21][CH:22]=2)[CH2:14]1)(=[O:5])=[O:4].[CH3:29][N:30]([CH3:35])[CH2:31][C:32](O)=[O:33].C(N(C(C)C)CC)(C)C.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>CN(C)C=O>[CH3:2][S:3]([O:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[CH:13]1[O:17][N:16]=[C:15]([C:18]2[N:19]=[C:20]([CH:23]3[CH2:28][CH2:27][N:26]([C:32](=[O:33])[CH2:31][N:30]([CH3:35])[CH3:29])[CH2:25][CH2:24]3)[S:21][CH:22]=2)[CH2:14]1)(=[O:4])=[O:5]

Participants

6

Reactant 4

HCID 673N,N-DimethylglycineHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 1178190674-[4-(5-{2-[(Methylsulphonyl)oxy]phenyl}-4,5-dihydro-1,2-oxazol-3-yl)-1,3-thiazol-2-yl]piperidinium chloride

Product 1

HCID 1178190312-(3-{2-[1-(N,N-Dimethylglycyl)piperidin-4-yl]-1,3-thiazol-4-yl}-4,5-dihydro-1,2-oxazol-5-yl)phenyl methanesulphonate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 4-[4-(5-{2-[(methylsulphonyl)oxy]phenyl}-4,5-dihydro-1,2-oxazol-3-yl)-1,3-thiazol-2-yl]piperidinium chloride (500 mg) in dimethylformamide (6 ml) under argon were added N,N-dimethylglycine (122 mg), diisopropylethylamine (582 mg) and O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TBTU, 542 mg). The reaction mixture was stirred at room temperature for 18 hours. Then ice-cold sodium hydrogencarbonate solution was added thereto, the mixture was filtered, and the aqueous phase was removed and extracted with ethyl acetate. The combined organic phases were dried over magnesium sulphate and concentrated. This gave 2-(3-{2-[1-(N,N-dimethylglycyl)piperidin-4-yl]-1,3-thiazol-4-yl}-4,5-dihydro-1,2-oxazol-5-yl)phenyl methanesulphonate (310 mg, 55%).

Workup

  1. additionThen ice-cold sodium hydrogencarbonate solution was added
  2. filtrationthe mixture was filtered
  3. customthe aqueous phase was removed
  4. extractionextracted with ethyl acetate
  5. dry with materialThe combined organic phases were dried over magnesium sulphate
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-8e6e7e98284546f48e199657a6bf6212
Source dataset
uspto-grants-2016_06
Patent number
US09375009B2

Reaction notes

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