Methyl 3-mercaptopropionate → Methyl 3-(5-(benzyloxy)-6-(4-methylthiazol-2-ylamino)pyridin-3-ylthio)propanoate

HRID 1426122Notes

Reaction equation

HRID 1426122 reaction equation
Cl.[CH2:2]([O:9][C:10]1[C:11]([NH:17][C:18]2[S:19][CH:20]=[C:21]([CH3:23])[N:22]=2)=[N:12][CH:13]=[C:14](Br)[CH:15]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(N(C(C)C)C(C)C)C.[SH:33][CH2:34][CH2:35][C:36]([O:38][CH3:39])=[O:37]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.O1CCOCC1>[CH2:2]([O:9][C:10]1[CH:15]=[C:14]([S:33][CH2:34][CH2:35][C:36]([O:38][CH3:39])=[O:37])[CH:13]=[N:12][C:11]=1[NH:17][C:18]1[S:19][CH:20]=[C:21]([CH3:23])[N:22]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

7

Reactant 3

HCID 18050Methyl 3-mercaptopropionateHCID 81531DiisopropylethylamineHCID 160614653-(benzyloxy)-5-bromo-N-(4-methylthiazol-2-yl)pyridin-2-amine hydrochloride

Product 1

HCID 16660505Methyl 3-(5-(benzyloxy)-6-(4-methylthiazol-2-ylamino)pyridin-3-ylthio)propanoateYield 78.5%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

A nitrogen purged 50 mL round-bottomed flask was charged with 3-(benzyloxy)-5-bromo-N-(4-methylthiazol-2-yl)pyridin-2-amine (prepared according to Example 1; 1.50 g, 3.99 mmol), Pd2dba3 (0.091 g, 0.099 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethyl-9H-xanthene (0.115 g, 0.199 mmol), and dioxane (20 mL). N-ethyl-N-isopropylpropan-2-amine (1.4 ml, 8.0 mmol) and methyl 3-mercaptopropanoate (0.49 mL, 4.4 mmol) were added and the flask was plunged into a 100° C. oil bath for 2 hours. The reaction mixture was cooled to room temperature and solvent removed. The residue was purified on silica gel (20 to 30% ethyl acetate/hexanes) to afford methyl 3-(5-(benzyloxy)-6-(4-methylthiazol-2-ylamino)pyridin-3-ylthio)propanoate (1.30 g, 78.5% yield) as a white solid. 1H NMR (CDCl3) δ 8.57 (bs, 1H), 8.04 (d, 1H), 7.41 (m, 5H), 7.22 (d, 1H), 6.42 (s, 1H), 5.12 (s, 2H), 3.68 (s, 3H), 3.03 (t, 2H), 2.56 (t, 2H), 2.32 (s, 3H); Mass spectrum (apci) m/z=325.0 (100) 416.0 (50).

Workup

  1. customA nitrogen purged 50 mL round-bottomed flask
  2. customwas plunged into a 100° C.
  3. customfor 2 hours
  4. customsolvent removed
  5. customThe residue was purified on silica gel (20 to 30% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-4a3c8f0e35df496b8a2c1a29e156ad0a
Source dataset
uspto-grants-2015_01
Patent number
US08933077B2

Reaction notes

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