Methanamine, N-methoxy-, hydrochloride (1:1) → HCID 86670376, compound

HRID 1972514Notes

Reaction equation

HRID 1972514 reaction equation
Cl.[S:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[S:7]([N:10]1[CH2:15][CH2:14][N:13]([C:16]2[CH:21]=[CH:20][C:19]([C:22]([OH:28])([CH3:27])[C:23]([F:26])([F:25])[F:24])=[CH:18][CH:17]=2)[C@@H:12]([CH2:29][C:30]([OH:32])=O)[CH2:11]1)(=[O:9])=[O:8].Cl.[CH3:34][NH:35][O:36][CH3:37].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O.O>[CH3:37][O:36][N:35]([CH3:34])[C:30](=[O:32])[CH2:29][C@H:12]1[CH2:11][N:10]([S:7]([C:3]2[S:2][CH:6]=[CH:5][CH:4]=2)(=[O:8])=[O:9])[CH2:15][CH2:14][N:13]1[C:16]1[CH:17]=[CH:18][C:19]([C:22]([OH:28])([CH3:27])[C:23]([F:25])([F:26])[F:24])=[CH:20][CH:21]=1

Participants

8

Reactant 4

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 70655426HCID 70655426, compound

Product 1

HCID 86670376HCID 86670376, compoundYield 94.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of ((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)acetic acid hydrochloride (1.55 g, 3.01 mmol), N,O-dimethylhydroxylamine hydrochloride (0.323 g, 3.31 mmol, Sigma-Aldrich, St. Louis, Mo.), and Hünig's base (1.05 mL, 6.02 mmol) in DMF (20 mL) was stirred at 0° C. To this mixture was added HATU (1.26 g, 3.31 mmol). The reaction was stirred for 3 h at room temperature and then diluted with EtOAc (30 mL) and water (20 mL). The organic layer was separated and then washed with water (2×20 mL) and brine (20 mL). The combined organic extracts were dried over MgSO4, filtered, and concentrated. The crude material was absorbed onto silica gel and purified via column chromatography (80 g silica gel, 0 to 100% EtOAc in hexanes) to give N-methoxy-N-methyl-2-((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)acetamide (1.48 g) as an orange oil.

Workup

  1. customThe organic layer was separated
  2. washwashed with water (2×20 mL) and brine (20 mL)
  3. dry with materialThe combined organic extracts were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was absorbed onto silica gel
  7. custompurified via column chromatography (80 g silica gel, 0 to 100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-35c8cb6abab94344a9f3fe71b7c3d1cf
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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