Methanol → Methyl 4-(2-(6-chloro-2-methylpyrimidin-4-ylamino)thiazol-5-ylthio)picolinate

HRID 1685358Notes

Reaction equation

HRID 1685358 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH:9][C:10]2[S:11][C:12]([S:15][C:16]#N)=[CH:13][N:14]=2)[CH:3]=1.SC[C@H:20]([C@@H:22]([CH2:24]S)O)[OH:21].C[C:27]1[C:28](C(N)=O)=[N:29]C=CC=1Cl.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH3:45][OH:46]>O.CN(C=O)C>[Cl:1][C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH:9][C:10]2[S:11][C:12]([S:15][C:16]3[CH:27]=[CH:28][N:29]=[C:22]([C:20]([O:46][CH3:45])=[O:21])[CH:24]=3)=[CH:13][N:14]=2)[CH:3]=1

Participants

8

Reactant 5

HCID 887MethanolHCID 62657Potassium Phosphate, TribasicHCID 446094D-1,4-DithiothreitolHCID 59200419N-(6-chloro-2-methylpyrimidin-4-yl)-5-thiocyanatothiazol-2-amineHCID 714331544-Chloro-3-methylpicolinamide

Product 1

HCID 59200387Methyl 4-(2-(6-chloro-2-methylpyrimidin-4-ylamino)thiazol-5-ylthio)picolinateYield 64%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of N-(6-chloro-2-methylpyrimidin-4-yl)-5-thiocyanatothiazol-2-amine (˜0.725 g, ˜2.56 mmol, crude, described in Synthesis of thiocyanates, Example C, Table 2) and dithiothreitol (373 mg, 2.418 mmol) in MeOH (12 mL) was stirred for 2 hours, then DMF (20 mL), methyl 4-chloro-2-picolinamide (202 mg, 1.177 mmol) and K3PO4 (127 mg, 0.597 mmol) were added. The reaction was stirred for 1.5 hours, then poured into water (˜125 mL) and allowed to sit overnight for complete precipitation. The solid was collected by filtration, washed with water and vacuum dried to afford the title material (299 mg, 64% over 2 steps) as a solid. 1H NMR (400 MHz, DMSO-d6) δ ppm: 12.39 (1H, s), 8.52 (1H, d, J=5.31 Hz), 7.91 (1H, s), 7.71 (1H, d, J=1.52 Hz), 7.37 (1H, dd, J=5.31, 2.02 Hz), 6.92 (1H, s), 3.82 (3H, s), 2.52 (3H, s). LC/MS (M+H)+: 394, 396. HPLC ret. time (Condition I): 1.652 min.

Workup

  1. customto sit overnight for complete precipitation
  2. filtrationThe solid was collected by filtration
  3. washwashed with water and vacuum
  4. customdried

Sources & evidence

ORD record
ord-1066debf1809447594c7724e2e2ef4c1
Source dataset
uspto-grants-2012_04
Patent number
US08148400B2

Reaction notes

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