Potassium Phosphate, Tribasic → Methyl 4-(2-(5-((tert-butoxycarbonylamino)methyl)pyridin-2-ylamino)thiazol-5-ylthio)-3-fluoropicolinate

HRID 1685344Notes

Reaction equation

HRID 1685344 reaction equation
[S:1]([C:4]1[S:8][C:7]([NH:9][C:10]2[N:15]=[CH:14][C:13]([CH2:16][NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[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:47]=[CH:46][N:45]=[C:44]([C:48]([O:50][CH3:51])=[O:49])[C:43]=1[F:52]>CO.CN(C=O)C>[C:20]([O:19][C:18]([NH:17][CH2:16][C:13]1[CH:12]=[CH:11][C:10]([NH:9][C:7]2[S:8][C:4]([S:1][C:2]3[CH:47]=[CH:46][N:45]=[C:44]([C:48]([O:50][CH3:51])=[O:49])[C:43]=3[F:52])=[CH:5][N:6]=2)=[N:15][CH:14]=1)=[O:24])([CH3:23])([CH3:22])[CH3:21]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 446094D-1,4-DithiothreitolHCID 59200355Methyl 4-chloro-3-fluoropicolinateHCID 59200436HCID 59200436, compound

Product 1

HCID 59200482Methyl 4-(2-(5-((tert-butoxycarbonylamino)methyl)pyridin-2-ylamino)thiazol-5-ylthio)-3-fluoropicolinateYield 92.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
23 °C

Procedure

Tert-butyl (6-(5-thiocyanatothiazol-2-ylamino)pyridin-3-yl)methylcarbamate (1.5 g, 4.13 mmol) was dissolved in methanol (30 mL) and treated with dithiothreitol (0.637 g, 4.13 mmol). The reaction was stirred at 23° C. for 1 hour. DMF (30 mL) was then added, followed by K3PO4 (0.351 g, 1.65 mmol) and methyl 4-chloro-3-fluoropicolinate (0.861 g, 4.53 mmol). The reaction was stirred at 23° C. for 1 hour, then methanol was evaporated. The title material was precipitated by adding water (˜200 mL), collected by filtration and dried under high vacuum to give the title material (1.875 g, 92%) as a solid. The compound was purified by silica gel chromatography (Biotage, dichloromethane/methanol) to give the title material as a solid. 1H NMR (400 MHz, DMSO-d6) δ ppm: 1.38 (9H, s) 3.91 (3H, s), 4.08 (2H, d, J=5.81 Hz), 7.09 (1H, d, J=8.34 Hz), 7.14 (1H, t, J=5.31 Hz), 7.41 (1H, t, J=5.94 Hz), 7.66 (1H, dd, J=8.46, 2.15 Hz), 7.82-7.85 (1H, m), 8.17 (1H, d, J=1.77 Hz), 8.33 (1H, d, J=5.05 Hz), 11.89 (1H, s). HPLC ret. time: 5.868 min. (Condition B).

Workup

  1. stirringThe reaction was stirred at 23° C. for 1 hour
  2. custommethanol was evaporated
  3. customThe title material was precipitated
  4. additionby adding water (˜200 mL)
  5. filtrationcollected by filtration
  6. customdried under high vacuum

Sources & evidence

ORD record
ord-8095b30e117f4c4682843be7d0866c15
Source dataset
uspto-grants-2012_04
Patent number
US08148400B2

Reaction notes

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