Toluene → HCID 46833786, compound

HRID 1516438Notes

Reaction equation

HRID 1516438 reaction equation
I[C:2]1[C:10]2[N:9]=[N:8][N:7]([C:11]3[CH:16]=[CH:15][N:14]=[C:13]([NH:17][CH:18]4[CH2:23][CH2:22][N:21]([S:24]([CH3:27])(=[O:26])=[O:25])[CH2:20][CH2:19]4)[N:12]=3)[C:6]=2[CH:5]=[CH:4][CH:3]=1.[CH3:28][C:29]1[C:30](B(O)O)=[CH:31][S:32][CH:33]=1.C([O-])([O-])=O.[Na+].[Na+].C1(C)C=CC=CC=1>CCO>[CH3:27][S:24]([N:21]1[CH2:22][CH2:23][CH:18]([NH:17][C:13]2[N:12]=[C:11]([N:7]3[C:6]4[CH:5]=[CH:4][CH:3]=[C:2]([C:30]5[C:29]([CH3:28])=[CH:33][S:32][CH:31]=5)[C:10]=4[N:9]=[N:8]3)[CH:16]=[CH:15][N:14]=2)[CH2:19][CH2:20]1)(=[O:26])=[O:25]

Participants

6

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 50839314-Methyl-3-thiopheneboronic acidHCID 67426785HCID 67426785, compound

Product 1

HCID 46833786HCID 46833786, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of [4-(4-iodobenzotriazol-1-yl)-pyrimidin-2-yl]-(1-methanesulfonyl-piperidin-4-yl)-amine (364 mg), 4-methyl-3-thiopheneboronic acid (109 mg) and Na2CO3 (2 M aq, 1.1 mL, degassed), toluene (13 mL, degassed) and EtOH (1 mL), was bubbled with argon and stirred at RT for 10 min in a screw cap pressure flask. To this was added Pd(PPh3)4 (25 mg), the flask sealed, and the mixture stirred overnight at 110° C. The reaction mixture was then cooled to RT, diluted in water, extracted in DCM, washed with water and brine, dried over Na2SO4, and the solvent stripped to yield a solid. The solid was chromatographed on silica, eluting with 0-30% Magic Base/DCM, then chromatographed again on silica using 0-100% EtOAc/hexanes. The product was titurated with Et2O, filtered, and evaporated in vacuo overnight to provide (1-methanesulfonyl-piperidin-4-yl)-{4-[4-(4-methyl-thiophen-3-yl)-benzotriazol-1-yl]-pyrimidin-2-yl}-amine (Compound 5, 219 mg). Mp=244.0-245.0° C.; M+H=470.

Workup

  1. customwas bubbled with argon
  2. customcap pressure flask
  3. additionTo this was added Pd(PPh3)4 (25 mg)
  4. customthe flask sealed
  5. stirringthe mixture stirred overnight at 110° C
  6. temperatureThe reaction mixture was then cooled to RT
  7. additiondiluted in water
  8. extractionextracted in DCM
  9. washwashed with water and brine
  10. dry with materialdried over Na2SO4
  11. customto yield a solid
  12. customThe solid was chromatographed on silica
  13. washeluting with 0-30% Magic Base/DCM
  14. customchromatographed again on silica using 0-100% EtOAc/hexanes
  15. filtrationfiltered
  16. customevaporated in vacuo overnight

Sources & evidence

ORD record
ord-acc69f8ec67746439eac9c5d31b2ab51
Source dataset
uspto-grants-2012_07
Patent number
US08227478B2

Reaction notes

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