Methyl 3-mercaptopropionate → HCID 68480265, compound

HRID 1511135Notes

Reaction equation

HRID 1511135 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:24][C:25]2[C:26]([CH3:32])=[N:27][N:28]([CH3:31])[C:29]=2[CH3:30])[C:5]([NH:8][C:9]2[S:13][N:12]=[C:11]([C@H:14]3[CH2:18][O:17][C:16]4([CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]4)[O:15]3)[N:10]=2)=[N:6][CH:7]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[SH:83][CH2:84][CH2:85][C:86]([O:88][CH3:89])=[O:87]>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].O>[O:15]1[C:16]2([CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)[O:17][CH2:18][C@@H:14]1[C:11]1[N:10]=[C:9]([NH:8][C:5]2[N:6]=[CH:7][C:2]([S:83][CH2:84][CH2:85][C:86]([O:88][CH3:89])=[O:87])=[CH:3][C:4]=2[O:24][C:25]2[C:26]([CH3:32])=[N:27][N:28]([CH3:31])[C:29]=2[CH3:30])[S:13][N:12]=1

Participants

7

Reactant 4

HCID 18050Methyl 3-mercaptopropionateHCID 62657Potassium Phosphate, TribasicHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 67485959HCID 67485959, compound

Product 1

HCID 68480265HCID 68480265, compoundYield 46.7%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A sealed tube was charged with (S)-N-(5-bromo-3-(1,3,5-trimethyl-1H-pyrazol-4-yloxy)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-amine (0.550 g, 1.055 mmol), Pd2(dba)3 (0.06065 g, 0.1055 mmol), K3PO4 (0.5821 g, 2.742 mmol), Xantphos (0.1221 g, 0.2110 mmol), and degassed toluene (5 mL). Nitrogen was bubbled through the solution for 5 minutes. Methyl 3-mercaptopropanoate (0.1752 ml, 1.582 mmol) was added and the reaction was heated to 100° C. overnight. The reaction was cooled to ambient temperature, water was added and the reaction was extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified over silica gel (50 to 100% ethyl acetate in hexanes) to afford (S)-methyl 3-(6-(3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-ylamino)-5-(1,3,5-trimethyl-1H-pyrazol-4-yloxy)pyridin-3-ylthio)propanoate (0.276 g, 0.4923 mmol, 46.67% yield) as yellow oil.

Workup

  1. customdegassed toluene (5 mL)
  2. customNitrogen was bubbled through the solution for 5 minutes
  3. temperatureThe reaction was cooled to ambient temperature
  4. extractionthe reaction was extracted with ethyl acetate
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified over silica gel (50 to 100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-af2efb957c014c99abae76b37f5f99b6
Source dataset
uspto-grants-2012_07
Patent number
US08212045B2

Reaction notes

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