4-Methylbenzylamine → HCID 9455491, compound

HRID 1019652Notes

Reaction equation

HRID 1019652 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@H:10]([C:14]([OH:16])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:41][C:42]1[CH:49]=[CH:48][C:45]([CH2:46][NH2:47])=[CH:44][CH:43]=1>C(Cl)Cl>[CH3:41][C:42]1[CH:49]=[CH:48][C:45]([CH2:46][NH:47][C:14]([C@H:10]2[CH2:11][CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:9]2)=[O:16])=[CH:44][CH:43]=1

Participants

5

Reactant 3

HCID 660354-MethylbenzylamineHCID 6951168(3S)-1-((tert-butoxy)carbonyl)piperidine-3-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 9455491HCID 9455491, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid (Beta Pharma Inc., 500 mg, 2.181 mmol) and TEA (0.912 mL, 6.54 mmol) in DCM (11 mL) was added HATU (912 mg, 2.399 mmol) followed by 4-methylbenzylamine (0.305 mL, 2.399 mmol). The resulting solution was stirred at room temperature for 48 hours. The reaction was concentrated, and the residue was adsorbed onto a plug of silica gel and purified by chromatography through a 50 g silica gel column, eluting with 0.5% to 5% MeOH in DCM, to provide M5.1 in 70% yield as a white foam. 1H NMR (300 MHz, CDCl3) δ ppm 7.08-7.20 (m, 4H), 6.13 (br. s., 1H), 4.38 (d, J=5.26 Hz, 2H), 3.92 (d, J=13.30 Hz, 1H), 3.62-3.83 (m, 1H), 3.21 (dd, J=13.01, 9.65 Hz, 1H), 3.00 (dd, J=10.40 Hz, 1H), 2.33 (s, 3H), 2.20-2.30 (m, 1H), 1.80-1.95 (m, 2H), 1.58-1.71 (m, 1H), 1.43-1.52 (m, 1H), 1.42 (s, 9H); ESI-MS M+Na 355.2.

Workup

  1. concentrationThe reaction was concentrated
  2. custompurified by chromatography through a 50 g silica gel column
  3. washeluting with 0.5% to 5% MeOH in DCM
  4. customto provide M5.1 in 70% yield as a white foam

Sources & evidence

ORD record
ord-6ef1418c9d8e46238150382315899fd5
Source dataset
uspto-grants-2014_05
Patent number
US08716281B2

Reaction notes

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