Hydrochloric Acid → N-(4-(3-(benzyloxy)phenoxy)pyridin-2-yl)-4-methylthiazol-2-amine

HRID 910968Notes

Reaction equation

HRID 910968 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]([NH:7][C:8]2[CH:13]=[C:12]([O:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3O)[CH:11]=[CH:10][N:9]=2)[S:5][CH:6]=1.[C:22](=[O:25])([O-])[O-].[K+].[K+].BrC[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.Cl>CCOCC.CN(C=O)C>[CH2:22]([O:25][C:17]1[CH:16]=[C:15]([CH:20]=[CH:19][CH:18]=1)[O:14][C:12]1[CH:11]=[CH:10][N:9]=[C:8]([NH:7][C:4]2[S:5][CH:6]=[C:2]([CH3:1])[N:3]=2)[CH:13]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 24826061(2-(4-Methylthiazol-2-ylamino)pyridin-4-yloxy)phenol

Product 1

HCID 24826501N-(4-(3-(benzyloxy)phenoxy)pyridin-2-yl)-4-methylthiazol-2-amineYield 38.4%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 6228DimethylformamideSolvent

Procedure

A mixture (2-(4-methylthiazol-2-ylamino)pyridin-4-yloxy)phenol (0.150 g, 0.501-mmol), potassium carbonate (0.208 g, 1.50 mmol), 1-(bromomethyl)benzene (0.0857 g, 0.501 mmol), and DMF (2 mL) was stirred overnight at room temperature. The reaction mixture was partitioned between ethyl acetate and water, and the ethyl acetate was washed with water and brine, dried and concentrated. The residue was purified via MPLC (Biotage) eluting with 7:3 hexane:ethyl acetate to afford the free base. The free base was dissolved in ether (4 mL) and 1M HCl in ether (1 mL) was added. The mixture was diluted with hexanes (5 mL) and triturated. The solids were collected by filtration, washed with hexanes, and dried to afford the desired product (0.075 g, 35.1% yield) as a white powder. 1H NMR (d6-DMSO) δ 10.5 (bs, 1H), 8.24 (d, 1H), 7.33-7.47 (m, 6H), 6.98 (d, 1H), 6.90 (s, 1H), 6.80 (d, 1H), 6.58-6.60 (m, 3H), 5.13 (s, 2H), 2.25 (s, 3H).

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and water
  2. washthe ethyl acetate was washed with water and brine
  3. customdried
  4. concentrationconcentrated
  5. customThe residue was purified via MPLC (Biotage)
  6. washeluting with 7:3 hexane
  7. customethyl acetate to afford the free base
  8. customtriturated
  9. filtrationThe solids were collected by filtration
  10. washwashed with hexanes
  11. customdried

Sources & evidence

ORD record
ord-d089f5acecdd48bfb8e9b96a90e482bf
Source dataset
uspto-grants-2011_09
Patent number
US08022222B2

Reaction notes

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