O-Methylhydroxylamine hydrochloride → HCID 86608266, compound

HRID 2233908Notes

Reaction equation

HRID 2233908 reaction equation
CN([C:4]([O:8][N:9]1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Cl:25][C:26]1[C:30]([Cl:31])=[C:29]([CH3:32])[NH:28][C:27]=1[C:33]([NH:35][CH:36]1[CH2:41][CH2:40][N:39]([C:42]2[N:47]=[C:46]([S:48][CH3:49])[N:45]=[C:44]([C:50]([OH:52])=O)[CH:43]=2)[CH2:38][CH2:37]1)=[O:34].Cl.O(N)C>CN(C=O)C.CCOC(C)=O.O>[Cl:25][C:26]1[C:30]([Cl:31])=[C:29]([CH3:32])[NH:28][C:27]=1[C:33]([NH:35][CH:36]1[CH2:37][CH2:38][N:39]([C:42]2[N:47]=[C:46]([S:48][CH3:49])[N:45]=[C:44]([C:50]([NH:9][O:8][CH3:4])=[O:52])[CH:43]=2)[CH2:40][CH2:41]1)=[O:34]

Participants

7

Reactant 3

HCID 521874O-Methylhydroxylamine hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68579500HCID 68579500, compound

Product 1

HCID 86608266HCID 86608266, compoundYield 81.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

HATU (197 mg, 0.52 mmol) was added to a solution of TEA (0.14 ml, 1.0 mmol), 6-(4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}piperidin-1-yl)-2-(methylthio)pyrimidine-4-carboxylic acid (Example 7, 230 mg, 0.52 mmol) and methoxylamine hydrochloride (43 mg, 0.52 mmol) in DMF (3 ml) under nitrogen. The resultant mixture was stirred overnight at room temperature, then diluted with EtOAc (50 ml) and water (10 ml) and the organic phase was separated. The organic phase was washed with 1 N HCl (5 ml), saturated NaHCO3 solution (5 ml) and brine (5 ml). The aqueous layers were back extracted with EtOAc (25 ml). The combined organic layers were dried over Na2SO4, filtered and concentrated under vacuum to give 400 mg of crude product. which was purified by preparative reversed-phase HPLC (water/acetonitrile gradient, 20-95%) to give 200 mg of the title compound.

Workup

  1. customthe organic phase was separated
  2. washThe organic phase was washed with 1 N HCl (5 ml), saturated NaHCO3 solution (5 ml) and brine (5 ml)
  3. extractionThe aqueous layers were back extracted with EtOAc (25 ml)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customto give 400 mg of crude product
  8. customwhich was purified by preparative reversed-phase HPLC (water/acetonitrile gradient, 20-95%)

Sources & evidence

ORD record
ord-8388343257b145f49f4c5524a034effe
Source dataset
uspto-grants-2010_05
Patent number
US07709503B2

Reaction notes

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