Hydrochloric Acid → 5-(2-chloropyridin-4-ylthio)-N-(4-methylthiazol-2-yl)-3-phenoxypyridin-2-amine dihydrochloride

HRID 335114Notes

Reaction equation

HRID 335114 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]([NH:7][C:8]2[N:13]=[CH:12][C:11]([S:14][CH2:15][CH2:16][C:17](OC)=O)=[CH:10][C:9]=2[O:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[S:5][CH:6]=1.[Cl:28][C:29]1[CH:34]=C([N+]([O-])=O)C=C[N:30]=1.CC([O-])(C)C.[K+].[NH4+].[Cl-:45].Cl>CS(C)=O>[ClH:28].[ClH:45].[Cl:28][C:29]1[CH:34]=[C:15]([S:14][C:11]2[CH:10]=[C:9]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:8]([NH:7][C:4]3[S:5][CH:6]=[C:2]([CH3:1])[N:3]=3)=[N:13][CH:12]=2)[CH:16]=[CH:17][N:30]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 25517Ammonium ChlorideHCID 7351522-Chloro-4-nitropyridineHCID 23665647Potassium tert-butoxideHCID 24765636Methyl 3-(6-(4-methylthiazol-2-ylamino)-5-phenoxypyridin-3-ylthio)propanoate

Product 1

HCID 866314795-(2-chloropyridin-4-ylthio)-N-(4-methylthiazol-2-yl)-3-phenoxypyridin-2-amine dihydrochlorideYield 41.4%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A mixture of methyl 3-(6-(4-methylthiazol-2-ylamino)-5-phenoxypyridin-3-ylthio)propanoate (72 mg, 0.18 mmol), 2-chloro-4-nitropyridine (85.3 mg, 0.54 mmol) and DMSO (2.0 mL) and purged with nitrogen for 5 minutes. Potassium 2-methylpropan-2-olate (60.4 mg, 0.54 mmol) was added and stirred for 30 minutes. The reaction was poured into aqueous NH4Cl and extracted with EtOAc (1×20 mL). The organic phase was washed with water, dried with sodium sulfate, filtered and concentrated. The residue was purified on silica gel (25% EtOAc in hexanes) to afford the title compound (37.1 mg, 41.4% yield) as a white solid after HCl salt formation. 1H NMR (CDCl3) δ 12.89 (bs, 1H), 8.24 (m, 2H), 8.17 (d, 1H), 7.43 (t, 2H), 7.31 (d, 1H), 7.28-7.18 (m, 3H), 6.88 (s, 1H), 6.84 (m, 1H), 6.53 (s, 1H), 3.93 (s, 1H), 2.50 (s, 3H). Mass spectrum (apci) m/z=427.2 (M+H-2HCl).

Workup

  1. custompurged with nitrogen for 5 minutes
  2. extractionextracted with EtOAc (1×20 mL)
  3. washThe organic phase was washed with water
  4. dry with materialdried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified on silica gel (25% EtOAc in hexanes)

Sources & evidence

ORD record
ord-07acad1064414880b2b60e9e5e973a69
Source dataset
uspto-grants-2014_11
Patent number
US08883828B2

Reaction notes

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