Ethanol → Methyl 3-(2-(3-(benzyloxy)-5-(2-chlorophenoxy)pyridin-2-ylamino)thiazol-4-yl)propanoate

HRID 1426169Notes

Reaction equation

HRID 1426169 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([NH:23][C:24]([NH2:26])=[S:25])=[N:11][CH:12]=[C:13]([O:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[Cl:22])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:28][C:29](=O)[CH2:30][CH2:31][C:32]([O:34][CH3:35])=[O:33].C(N(CC)CC)C.C(O)C>C(OCC)(=O)C>[CH2:1]([O:8][C:9]1[C:10]([NH:23][C:24]2[S:25][CH:28]=[C:29]([CH2:30][CH2:31][C:32]([O:34][CH3:35])=[O:33])[N:26]=2)=[N:11][CH:12]=[C:13]([O:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[Cl:22])[CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 702EthanolHCID 8471TriethylamineHCID 9855825Methyl 5-bromo-4-oxopentanoateHCID 86639702HCID 86639702, compound

Product 1

HCID 59225711Methyl 3-(2-(3-(benzyloxy)-5-(2-chlorophenoxy)pyridin-2-ylamino)thiazol-4-yl)propanoateYield 71.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 1-(3-(benzyloxy)-5-(2-chlorophenoxy)pyridin-2-yl)thiourea (0.471 g, 1.11 mmol), methyl 5-bromo-4-oxopentanoate (0.279 g, 1.33 mmol), triethylamine (0.271 ml, 1.94 mmol), and ethanol (10 mL) was heated at reflux for 2 hours, cooled, partitioned between ethyl acetate and 2N NaOH, washed with water and brine, dried, and concentrated. The residue was purified by MPLC (Biotage) eluting with 3:1 hexane:ethyl acetate to afford methyl 3-(2-(3-(benzyloxy)-5-(2-chlorophenoxy)pyridin-2-ylamino)thiazol-4-yl)propanoate (0.392 g, 71.2% yield) as a white viscous oil/wax. The compound (70 mg) was dissolved in ether (2 mL) and 1N HCl in ether (0.5 mL) was added. The mixture was stirred 5 minutes, and hexanes (5 mL) were added. The mixture was decanted, and a mixture of hexanes:ether (2:1, 3 mL) was added three times with three decantations. The solid material was dried to afford methyl 3-(2-(3-(benzyloxy)-5-(2-chlorophenoxy)pyridin-2-ylamino)thiazol-4-yl)propanoate hydrochloride (0.058 g, 9.81% yield) as a white solid. 1H NMR (DMSO-d6) δ 2.73 (t, 2H), 3.61 (s, 3H), 2.91 (t, 2H), 5.32 (s, 2H), 6.82 (s, 1H), 6.99 (d, 1H), 7.21 (t, 1H), 7.31-7.43 (m, 4H), 7.47 (d, 1H), 7.55-7.66 (m, 5H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 2 hours
  3. temperaturecooled
  4. custompartitioned between ethyl acetate and 2N NaOH
  5. washwashed with water and brine
  6. customdried
  7. concentrationconcentrated
  8. customThe residue was purified by MPLC (Biotage)
  9. washeluting with 3:1 hexane

Sources & evidence

ORD record
ord-90488787c78341738f3c59729ec7d698
Source dataset
uspto-grants-2015_01
Patent number
US08933077B2

Reaction notes

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