Water → Tert-butyl 2-(3-((2-(4-methylthiazol-2-ylamino)pyridin-3-yloxy)methyl)phenoxy)acetate

HRID 1426109Notes

Reaction equation

HRID 1426109 reaction equation
Cl.[CH3:2][C:3]1[N:4]=[C:5]([NH:8][C:9]2[C:14]([O:15][CH2:16][C:17]3[CH:18]=[C:19]([OH:23])[CH:20]=[CH:21][CH:22]=3)=[CH:13][CH:12]=[CH:11][N:10]=2)[S:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33].O>CN(C=O)C>[CH3:2][C:3]1[N:4]=[C:5]([NH:8][C:9]2[C:14]([O:15][CH2:16][C:17]3[CH:18]=[C:19]([CH:20]=[CH:21][CH:22]=3)[O:23][CH2:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])=[CH:13][CH:12]=[CH:11][N:10]=2)[S:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 79177tert-Butyl bromoacetateHCID 866396593-((2-(4-Methylthiazol-2-ylamino)pyridin-3-yloxy)methyl)phenol hydrochloride

Product 1

HCID 59225697Tert-butyl 2-(3-((2-(4-methylthiazol-2-ylamino)pyridin-3-yloxy)methyl)phenoxy)acetateYield 55.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-((2-(4-Methylthiazol-2-ylamino)pyridin-3-yloxy)methyl)phenol (prepared according to Example 22; 900 mg, 2.87 mmol), potassium carbonate (992 mg, 7.18 mmol), and tert-butyl 2-bromoacetate (0.424 mL, 2.87 mmol) were added to a 100 mL round bottom flask and dissolved in DMF (10 mL). The reaction mixture was stirred for 3 hours, then water (90 mL) was added and the reaction mixture was stirred at room temperature for 1 hour. The resultant solids were filtered and purified over silica gel (20% ethyl acetate in hexanes) to afford tert-butyl 2-(3-((2-(4-methylthiazol-2-ylamino)pyridin-3-yloxy)methyl)phenoxy)acetate (680 mg, 55.4% yield) as a white foam. 1H NMR (CDCl3) δ 8.60 (bs, 1H), 7.94 (dd, 1H), 7.32 (t, 1H), 7.07 (dd, 1H), 7.03 (m, 1H), 6.95 (m, 1H), 6.89 (dd, 1H), 6.80 (dd, 1H), 6.39 (q, 1H), 5.08 (s, 2H), 4.53 (s, 2H), 2.33 (s, 3H), 1.48 (s, 9H). Mass spectrum (apci) m/z=372 (100), 428 (20).

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 1 hour
  2. filtrationThe resultant solids were filtered
  3. custompurified over silica gel (20% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-f1136512ee18466a9510aa3ff3cbe393
Source dataset
uspto-grants-2015_01
Patent number
US08933077B2

Reaction notes

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