Hydrochloric Acid → N-(4-methylthiazol-2-yl)-3-phenoxy-5-(pyridin-2-ylmethylthio)pyridin-2-amine dihydrochloride

HRID 1806016Notes

Reaction equation

HRID 1806016 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.CC([O-])(C)C.[K+].Br.BrC[C:37]1[CH:42]=[CH:41]C=C[N:38]=1.[Cl-:43].[NH4+].Cl>C1COCC1>[ClH:43].[ClH:43].[CH3:1][C:2]1[N:3]=[C:4]([NH:7][C:8]2[C:9]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[CH:10][C:11]([S:14][CH2:15][C:16]3[CH:17]=[CH:41][CH:42]=[CH:37][N:38]=3)=[CH:12][N:13]=2)[S:5][CH:6]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 25517Ammonium ChlorideHCID 27347202-(Bromomethyl)pyridine hydrobromideHCID 23665647Potassium tert-butoxideHCID 24765636Methyl 3-(6-(4-methylthiazol-2-ylamino)-5-phenoxypyridin-3-ylthio)propanoate

Product 1

HCID 24765641N-(4-methylthiazol-2-yl)-3-phenoxy-5-(pyridin-2-ylmethylthio)pyridin-2-amine dihydrochlorideYield 60.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A 20 mL vial was charged with methyl 3-(6-(4-methylthiazol-2-ylamino)-5-phenoxypyridin-3-ylthio)propanoate (135.8 mg, 0.338 mmol) and THF (0.5 mL). 1M KOtBu in THF (1.184 mL, 1.184 mmol) was added and the reaction mixture was stirred at room temperature for 30 seconds. 2-(Bromomethyl)pyridine hydrobromide (85.55 mg, 0.3382 mmol) was added and the reaction mixture was stirred at room temperature for 30 minutes. Saturated aqueous ammonium chloride was added and the reaction mixture was extracted with EtOAc. The concentrated residue was purified on silica gel to afford N-(4-methylthiazol-2-yl)-3-phenoxy-5-(pyridin-2-ylmethylthio)pyridin-2-amine dihydrochloride (98.2 mg, 60.5% yield) as a pale yellow solid after HCl salt formation. 1H NMR (d6-DMSO) δ 8.66 (dd, 1H), 8.22 (td, 1H), 8.12 (d, 1H), 7.70 (t, 1H), 7.62 (d, 1H), 7.45 (m, 2H), 7.23 (t, 1H), 7.16 (d, 1H), 7.06 (m, 2H), 6.82 (m, 1H), 4.42 (s, 2H), 2.29 (s, 3H); Mass spectrum (esi) m/z=407.2 (100) (M+H-2HCl).

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 30 minutes
  2. extractionthe reaction mixture was extracted with EtOAc
  3. customThe concentrated residue was purified on silica gel

Sources & evidence

ORD record
ord-b47b152f4861434899ec4d1ea84df2a1
Source dataset
uspto-grants-2013_01
Patent number
US08354540B2

Reaction notes

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