2-Amino-5-methylpyridine → (S)-4-methoxy-1-(5-methylpyridin-2-ylamino)-1-oxobutan-2-yl acetate

HRID 1098120Notes

Reaction equation

[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([NH2:8])=[N:6][CH:7]=1.[C:9]([O:12][C@@H:13]([CH2:17][CH2:18][O:19][CH3:20])[C:14](O)=[O:15])(=[O:11])[CH3:10].O.[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1>C1COCC1>[C:9]([O:12][C@@H:13]([CH2:17][CH2:18][O:19][CH3:20])[C:14]([NH:8][C:5]1[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][N:6]=1)=[O:15])(=[O:11])[CH3:10]

Participants

Conditions

Temperature: 23 °C

Procedure

5-Methylpyridin-2-amine (CAS no. 1603-41-4) (460 mg, 4.26 mmol) was added to (S)-2-acetoxy-4-methoxybutanoic acid (Intermediate F3) (500 mg, 2.84 mmol), in THF (8 mL) under nitrogen. The resulting suspension was stirred at 23° C. for 30 minutes. 4-(4,6-Dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrate (CAS no. 3945-69-5) (1.18 g, 4.26 mmol) was added and the suspension stirred for 40 hrs. The reaction mixture was concentrated and purified by flash silica chromatography, elution gradient 0 to 50% EtOAc in isohexane to afford (S)-4-methoxy-1-(5-methylpyridin-2-ylamino)-1-oxobutan-2-yl acetate (410 mg, 54%). 1H NMR (400 MHz, CDCl3) δ 2.13-2.28 (5H, m), 2.30 (3H, s), 3.31 (3H, s), 3.48-3.53 (2H, m), 5.37-5.40 (1H, m), 7.50-7.53 (1H, m), 8.09-8.11 (2H, m), 8.52 (1H, s); m/z (ESI+) (M+H)+=267; HPLC tR=1.22 min.

Workup

addition3945-69-5) (1.18 g, 4.26 mmol) was added
stirringthe suspension stirred for 40 hrs
concentrationThe reaction mixture was concentrated
custompurified by flash silica chromatography, elution gradient 0 to 50% EtOAc in isohexane

Sources & evidence

ORD record: ord-a34063dbb52c432bacd69b3fb87c91be
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08143263B2

Reaction notes

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