Methyl 3-mercaptopropionate → Methyl 3-(6-(4-(1-acetylpiperidin-4-yl)thiazol-2-ylamino)-5-phenoxypyridin-3-ylthio)propanoate

HRID 1809557Notes

Reaction equation

HRID 1809557 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:5]([NH:8][C:9]2[S:10][CH:11]=[C:12]([CH:14]3[CH2:19][CH2:18][N:17]([C:20](=[O:22])[CH3:21])[CH2:16][CH2:15]3)[N:13]=2)=[N:6][CH:7]=1.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.[SH:72][CH2:73][CH2:74][C:75]([O:77][CH3:78])=[O:76].C(N(C(C)C)C(C)C)C>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].O1CCOCC1>[C:20]([N:17]1[CH2:18][CH2:19][CH:14]([C:12]2[N:13]=[C:9]([NH:8][C:5]3[N:6]=[CH:7][C:2]([S:72][CH2:73][CH2:74][C:75]([O:77][CH3:78])=[O:76])=[CH:3][C:4]=3[O:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[S:10][CH:11]=2)[CH2:15][CH2:16]1)(=[O:22])[CH3:21]

Participants

7

Reactant 4

HCID 18050Methyl 3-mercaptopropionateHCID 81531DiisopropylethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 249445171-(4-(2-(5-Bromo-3-phenoxypyridin-2-ylamino)thiazol-4-yl)piperidin-1-yl)ethanone

Product 1

HCID 86631532Methyl 3-(6-(4-(1-acetylpiperidin-4-yl)thiazol-2-ylamino)-5-phenoxypyridin-3-ylthio)propanoate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 1-(4-(2-(5-Bromo-3-phenoxypyridin-2-ylamino)thiazol-4-yl)piperidin-1-yl)ethanone (40.0 g, 84.5 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethyl-9H-xanthene (2.44 g, 4.22 mmol), Pd2dba3 (1.93 g, 2.11 mmol), methyl 3-mercaptopropanoate (18.7 mL, 169 mmol), N-ethyl-N-isopropylpropan-2-amine (15.4 mL, 88.7 mmol), and dioxane (250 mL) was heated to 95° C. under nitrogen for 2 hours. The reaction was cooled to ambient temperature and the resultant solids were filtered through celite washing with CH2Cl2. The filtrate was concentrated to a yellow oil and purified on silica eluting with 3%-5% MeOH/EtOAc to afford methyl 3-(6-(4-(1-acetylpiperidin-4-yl)thiazol-2-ylamino)-5-phenoxypyridin-3-ylthio)propanoate as a yellow oil.

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. filtrationthe resultant solids were filtered
  3. washthrough celite washing with CH2Cl2
  4. concentrationThe filtrate was concentrated to a yellow oil
  5. custompurified on silica eluting with 3%-5% MeOH/EtOAc

Sources & evidence

ORD record
ord-f980f394f53a42249d90c79d895fad74
Source dataset
uspto-grants-2013_01
Patent number
US08362037B2

Reaction notes

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