Methyl 3-mercaptopropionate → HCID 66995289, compound

HRID 1809562Notes

Reaction equation

HRID 1809562 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:5]([NH:8][C:9]2[S:13][N:12]=[C:11]([CH:14]3[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]3)[N:10]=2)=[N:6][CH:7]=1.C(N(C(C)C)C(C)C)C.[SH:43][CH2:44][CH2:45][C:46]([O:48][CH3:49])=[O:47]>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>[CH3:49][O:48][C:46](=[O:47])[CH2:45][CH2:44][S:43][C:2]1[CH:3]=[C:4]([O:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:5]([NH:8][C:9]2[S:13][N:12]=[C:11]([CH:14]3[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]3)[N:10]=2)=[N:6][CH:7]=1

Participants

7

Reactant 3

HCID 18050Methyl 3-mercaptopropionateHCID 81531DiisopropylethylamineHCID 66995367HCID 66995367, compound

Product 1

HCID 66995289HCID 66995289, compoundYield 69.1%

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

Conditions

Temperature
95 °C

Procedure

A 1 L flask was charged with tert-butyl 4-(5-(5-bromo-3-phenoxypyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)piperidine-1-carboxylate (Example 4, Step D, 24.4 g, 45.8 mmol), N-ethyl-N-isopropylpropan-2-amine (16.0 mL, 91.7 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethyl-9H-xanthene (1.33 g, 2.29 mmol), and dioxane (450 mL). Nitrogen was bubbled through the solution for 30 minutes. Methyl 3-mercaptopropanoate (5.46 mL, 50.4 mmol) and Pd2dba3 (1.05 g, 1.15 mmol) were added and the reaction was heated at 95° C. overnight. The reaction was cooled to ambient temperature and the resultant solids were filtered through celite. The filtrate was concentrated and purified on silica (30 to 40% EtOAc in hexanes) to afford tert-butyl 4-(5-(5-(3-methoxy-3-oxopropylthio)-3-phenoxypyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)piperidine-1-carboxylate (18.1 g, 69.1% yield) as a white foam.

Workup

  1. customNitrogen was bubbled through the solution for 30 minutes
  2. temperatureThe reaction was cooled to ambient temperature
  3. filtrationthe resultant solids were filtered through celite
  4. concentrationThe filtrate was concentrated
  5. custompurified on silica (30 to 40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-76dbdb320281444bad5de631d4d4f6a8
Source dataset
uspto-grants-2013_01
Patent number
US08362037B2

Reaction notes

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