Methyl 3-mercaptopropionate → (S)-methyl 3-(6-(3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-ylamino)-5-(2-methylpyridin-3-yloxy)pyridin-3-ylthio)propanoate

HRID 534033Notes

Reaction equation

HRID 534033 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:24][C:25]2[C:26]([CH3:31])=[N:27][CH:28]=[CH:29][CH:30]=2)[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.[SH:32][CH2:33][CH2:34][C:35]([O:37][CH3:38])=[O:36].C(N(CC)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]>[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:32][CH2:33][CH2:34][C:35]([O:37][CH3:38])=[O:36])=[CH:3][C:4]=2[O:24][C:25]2[C:26]([CH3:31])=[N:27][CH:28]=[CH:29][CH:30]=2)[S:13][N:12]=1

Participants

5

Reactant 3

HCID 18050Methyl 3-mercaptopropionateHCID 81531DiisopropylethylamineHCID 67486320(S)-N-(5-bromo-3-(2-methylpyridin-3-yloxy)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-amine

Product 1

HCID 67487943(S)-methyl 3-(6-(3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-ylamino)-5-(2-methylpyridin-3-yloxy)pyridin-3-ylthio)propanoateYield 68.9%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

To a solution of (S)-N-(5-bromo-3-(2-methylpyridin-3-yloxy)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-amine (3.1 g, 6.14 mmol) in dioxanes (30 mL) continuously purged with nitrogen was added Xanphos (0.177 g, 0.303 mmol). Pd2dba3 (0.14 g, 0.153 mmol), methyl 3-mercaptopropanoate (0.73 g, 6.14 mmol) and N,N-diisopropylethylamine (1.17 mL, 6.45 mmol) and the reaction was heated overnight at 80° C. The reaction was concentrated in vacuo and the residue purified over silica gel (5% MeOH/CH2Cl2) to afford (S)-methyl 3-(6-(3-(1,4-dioxaspiro[4.5]decane-2-yl)-1,2,4-thiadiazol-5-ylamino)-5-(2-methylpyridin-3-yloxy)pyridin-3-ylthio)propanoate (2.3 g, 68%).

Workup

  1. additionwas added Xanphos (0.177 g, 0.303 mmol)
  2. concentrationThe reaction was concentrated in vacuo
  3. customthe residue purified over silica gel (5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-03bd2a0f786a42b8b2cc176d0f52b363
Source dataset
uspto-grants-2014_10
Patent number
US08853409B2

Reaction notes

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