Dichloromethane → Tert-butyl 3-((4-(5-amino-6-(5-phenyl-1,3,4-thiadiazol-2-yl)pyrazin-2-yl)phenyl)sulfonyl)piperidine-1-carboxylate

HRID 78728Notes

Reaction equation

HRID 78728 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][C:12]([S:15]([CH:18]3[CH2:23][CH2:22][CH2:21][N:20]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:19]3)(=[O:17])=[O:16])=[CH:11][CH:10]=2)O1.Br[C:33]1[N:34]=[C:35]([C:40]2[S:41][C:42]([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)=[N:43][N:44]=2)[C:36]([NH2:39])=[N:37][CH:38]=1.C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:39][C:36]1[N:37]=[CH:38][C:33]([C:9]2[CH:10]=[CH:11][C:12]([S:15]([CH:18]3[CH2:23][CH2:22][CH2:21][N:20]([C:24]([O:26][C:27]([CH3:28])([CH3:30])[CH3:29])=[O:25])[CH2:19]3)(=[O:17])=[O:16])=[CH:13][CH:14]=2)=[N:34][C:35]=1[C:40]1[S:41][C:42]([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)=[N:43][N:44]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 594718915-Bromo-3-(5-phenyl-1,3,4-thiadiazol-2-yl)pyrazin-2-amineHCID 86682773Tert-butyl 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]sulfonylpiperidine-1-carboxylate

Product 1

HCID 86682784Tert-butyl 3-((4-(5-amino-6-(5-phenyl-1,3,4-thiadiazol-2-yl)pyrazin-2-yl)phenyl)sulfonyl)piperidine-1-carboxylateYield 100%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of tert-butyl 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]sulfonylpiperidine-1-carboxylate (162.0 mg, 0.3590 mmol), 5-bromo-3-(5-phenyl-1,3,4-thiadiazol-2-yl)pyrazin-2-amine (100 mg, 0.2992 mmol), Pd(dppf)Cl2.DCM (24.43 mg, 0.02992 mmol) and Na2CO3 (448.8 μL of 2 M, 0.8976 mmol) in dioxane (2 mL) was irradiated by microwave at 100° C. for 30 minutes. The mixture was diluted with water and the aqueous layer was extracted with EtOAc (×2). The combined organic extracts were washed with brine (×1), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (ISCO Companion, 24 g column, eluting with 0 to 50% EtOAc/Petroleum Ether, loaded in DCM) to give the sub-title product as a yellow solid (173 mg, 100% Yield). 1H NMR (400.0 MHz, DMSO-d6) δ 9.04 (s, 1H), 8.36 (d, 2H), 8.16 (br s, 2H), 8.13 (dd, 2H), 8.01 (d, 2H), 7.64-7.61 (m, 3H), 4.10-3.95 (m, 1H), 3.76 (br d, 1H), 2.99-2.74 (m, 2H), 2.12-2.02 (m, 1H), 1.75-1.59 (m, 2H) and 1.35-1.32 (m, 11H) ppm; LC/MS m/z 579.2 [M+1]+.

Workup

  1. extractionthe aqueous layer was extracted with EtOAc (×2)
  2. washThe combined organic extracts were washed with brine (×1)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography (ISCO Companion, 24 g column, eluting with 0 to 50% EtOAc/Petroleum Ether, loaded in DCM)

Sources & evidence

ORD record
ord-176aac714985482397aa43a484a39936
Source dataset
uspto-grants-2014_09
Patent number
US08841449B2

Reaction notes

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