Sodium Bicarbonate → (S)-4-chloro-1-(1-methoxymethyl-3-methoxypropyl)-6-methyl-1H-1,2,3-triazolo[4,5-c]pyridine

HRID 1279268Notes

Reaction equation

[NH2:1][C:2]1[C:3]([Cl:18])=[N:4][C:5]([CH3:17])=[CH:6][C:7]=1[NH:8][CH:9]([CH2:14][O:15][CH3:16])[CH2:10][CH2:11][O:12][CH3:13].[N:19]([O-])=O.[Na+].C([O-])(O)=O.[Na+]>C(Cl)Cl.C(O)(=O)C.O>[Cl:18][C:3]1[C:2]2[N:1]=[N:19][N:8]([C@H:9]([CH2:14][O:15][CH3:16])[CH2:10][CH2:11][O:12][CH3:13])[C:7]=2[CH:6]=[C:5]([CH3:17])[N:4]=1

Participants

Conditions

Temperature: 0 °C

Procedure

3-amino-2-chloro-6-methyl-4-N-(1-methoxymethyl-3-methoxypropyl)pyridin-4-amine (4.1 g, 14.98 mmol) was dissolved in a mixture of CH2Cl2 (40 mL) and 50% acetic acid (40 mL) and cooled to 0° C. in an ice bath. To that a solution of NaNO2 (1.84 g, 26.86 mmol) in water (10 mL) was added dropwise and the reaction was stirred at 0° C. for 30 min and at 25° C. for 1.5 h. Then the acetic acid was neutralized with solid NaHCO3 and water (80 mL) was added. The mixture was extracted with EtOAc (2×100 mL) and the combined organic extracts were combined and washed with brine (50 mL), dried and stripped in vacuo. The residue was chromatographed on silica gel (40% EtOAc/hexanes eluent) to give the product (4.05 g, 56% overall for the eight steps). NMR(CDCl3)d 7.25 (s, 1H), 5.04-5.13 (m, 1H), 3.98 (dd, 1H, J1=9.9 Hz, J2=8.4 Hz), 3.84 (dd, 1H, J1=10.2 Hz, J2=4.4 Hz), 3.39 (dt, 1H, J1=9.9 Hz, J2=4.8 Hz), 3.25 (s, 3H), 3.17 (s, 3H), 2.91 (dt, 1H, J1=9.5 Hz, J2=4.0 Hz), 2.68 (s, 3H), 2.22-2.6 (m, 2H).

Workup

additionwas added
extractionThe mixture was extracted with EtOAc (2×100 mL)
washwashed with brine (50 mL)
customdried
customThe residue was chromatographed on silica gel (40% EtOAc/hexanes eluent)
customto give the product (4.05 g, 56% overall for the eight steps)

Sources & evidence

ORD record: ord-8b4cbed6b4cf491a8574a89200fe042c
Source dataset: uspto-grants-2002_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06448261B1

Reaction notes

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