Potassium Phosphate, Tribasic → Methyl 3-fluoro-4-(2-(5-(hydroxymethyl)pyridin-2-ylamino)thiazol-5-ylthio)picolinate

HRID 1685342Notes

Reaction equation

[S:1]([C:4]1[S:8][C:7]([NH:9][C:10]2[N:15]=[CH:14][C:13]([CH2:16][OH:17])=[CH:12][CH:11]=2)=[N:6][CH:5]=1)[C:2]#N.SC[C@H]([C@@H](CS)O)O.[O-]P([O-])([O-])=O.[K+].[K+].[K+].ClC1[CH:40]=[CH:39][N:38]=[C:37]([C:41]([O:43][CH3:44])=[O:42])[C:36]=1[F:45]>CO.CN(C=O)C>[F:45][C:36]1[C:37]([C:41]([O:43][CH3:44])=[O:42])=[N:38][CH:39]=[CH:40][C:2]=1[S:1][C:4]1[S:8][C:7]([NH:9][C:10]2[CH:11]=[CH:12][C:13]([CH2:16][OH:17])=[CH:14][N:15]=2)=[N:6][CH:5]=1

Participants

Conditions

Temperature: 23 °C

Procedure

(6-(5-Thiocyanatothiazol-2-ylamino)pyridin-3-yl)methanol (1.0 g, 3.78 mmol) was dissolved in methanol (30 mL) and treated with dithiothreitol (0.582 g, 3.78 mmol). The reaction was stirred at 23° C. for 1 hour. DMF (30 mL) was then added, followed by K3PO4 (0.321 g, 1.51 mmol) and methyl 4-chloro-3-fluoropicolinate (0.788 g, 4.16 mmol). The reaction was stirred at 23° C. for 1 hour, then methanol was evaporated. The title material was precipitated by adding water (˜150 mL), collected by filtration and dried under high vacuum to give the title material (1.287 g, 87%) as a solid. 1H NMR (400 MHz, DMSO-d6) δ ppm: 3.34 (2H, s), 4.46 (2H, d, J=5.05 Hz) 5.22 (1H, t, J=5.56 Hz), 7.10 (1H, d, J=8.34 Hz), 7.15 (1H, t, J=5.31 Hz), 7.74 (1H, dd, J=8.59, 2.27 Hz), 7.84 (1H, s), 8.24 (1H, d, J=1.52 Hz), 8.33 (1H, d, J=5.05 Hz), 11.89 (1H, s). LC/MS (M+H)+: 393. HPLC ret. time (Condition N): 4.319 min.

Workup

stirringThe reaction was stirred at 23° C. for 1 hour
custommethanol was evaporated
customThe title material was precipitated
additionby adding water (˜150 mL)
filtrationcollected by filtration
customdried under high vacuum

Sources & evidence

ORD record: ord-bdd753379d8c41bead3acb016b1fb4ff
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08148400B2

Reaction notes

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