Methylamine → HCID 86723932, compound

HRID 1475287Notes

Reaction equation

HRID 1475287 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:13]([CH3:14])[CH2:12][N:11]([C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])[C@@H:10]([C:25](O)=[O:26])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:28][N:29](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.CN.C1COCC1>CN(C=O)C.O>[C:1]([O:5][C:6]([N:8]1[CH2:9][C@H:10]([C:25](=[O:26])[NH:29][CH3:28])[N:11]([C:15]([O:17][CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[O:16])[CH2:12][C@H:13]1[CH3:14])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 5

HCID 6329MethylamineHCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 71003225HCID 71003225, compound

Product 1

HCID 86723932HCID 86723932, compoundYield 58%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

(2R,5R)-5-Methyl-piperazine-1,2,4-tricarboxylic acid 1-benzyl ester 4-tert-butyl ester (200 mg, 0.53 mmol) was dissolved in anhydrous DMF (2.65 mL). HATU (221 mg, 0.58 mol) was added and the reaction stirred for 20 min. DIPEA (184 μL, 1.06 mmol) and methylamine in THF (2.0M, 0.53 mL, 1.06 mmol) were added and the reaction stirred for 2 h. Water (10 mL) was added and aqueous phase extracted with EtOAc (3×5.0 mL). The combined organic extracts were washed with saturated aqueous sodium bicarbonate (3×15 mL), brine (3×15 mL), dried over sodium sulfate, filtered and concentrated. Column chromatography on silica gel (gradient elution, 0-100% EtOAc/petrol), gave the title compound (0.12 g, 58%) as a colourless oil. 1H NMR (Me-d3-OD): 7.48-7.26 (5H, m), 5.30-5.04 (2H, m), 4.44 (1H, d), 4.21 (2H, s), 3.64 (2H, d), 3.44 (1H, d), 2.72 (3H, d), 1.46 (9H, s), 1.16 (3H, dd).

Workup

  1. stirringthe reaction stirred for 2 h
  2. extractionaqueous phase extracted with EtOAc (3×5.0 mL)
  3. washThe combined organic extracts were washed with saturated aqueous sodium bicarbonate (3×15 mL), brine (3×15 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-30d8996fb97c4a78bafdbf57ffb089c8
Source dataset
uspto-grants-2015_04
Patent number
US09018214B2

Reaction notes

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