Toluene → HCID 46833788, compound

HRID 1516439Notes

Reaction equation

HRID 1516439 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([CH:10]2[CH2:15][CH2:14][CH:13]([NH:16][C:17]3[N:22]=[C:21]([N:23]4[C:27]5[CH:28]=[CH:29][CH:30]=[C:31](I)[C:26]=5[N:25]=[N:24]4)[CH:20]=[CH:19][N:18]=3)[CH2:12][CH2:11]2)=[O:9])[CH2:4][CH2:3]1.[S:33]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34]1.C([O-])([O-])=O.[Na+].[Na+].C1(C)C=CC=CC=1>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCO>[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([CH:10]2[CH2:15][CH2:14][CH:13]([NH:16][C:17]3[N:22]=[C:21]([N:23]4[C:27]5[CH:28]=[CH:29][CH:30]=[C:31]([C:35]6[CH:36]=[CH:37][S:33][CH:34]=6)[C:26]=5[N:25]=[N:24]4)[CH:20]=[CH:19][N:18]=3)[CH2:12][CH2:11]2)=[O:9])[CH2:4][CH2:3]1

Participants

8

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 581760Thiophene-3-boronic acidHCID 67425529HCID 67425529, compound

Product 1

HCID 46833788HCID 46833788, compoundYield 79.7%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of (4-hydroxy-piperidin-1-yl)-{4-[4-(4-iodobenzotriazol-1-yl)-pyrimidin-2-yl-amino]-cyclohexyl}-methanone (274 mg) and 3-thiopheneboronic acid (67 mg) was placed in a screw cap pressure flask, and Na2CO3 (2 M aq, 0.7 mL, degassed), toluene (5 mL, degassed) and EtOH (5 mL), added. To this was added Pd(PPh3)4 (20 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 crude solid (0.25 g). The crude product was chromatographed on silica, and eluted with 0-70% Magic Base/DCM, titurated in Et2O, filtered, and evaporated to yield (4-hydroxy-piperidin-1-yl)-{4-[4-(4-thiophen-3-ylbenzotriazol-1-yl)-pyrimidin-2-ylamino]-cyclohexyl}-methanone (Compound 6, 201 mg). mp=233-234° C.; M+H=504.

Workup

  1. customcap pressure flask
  2. customthe flask sealed
  3. temperatureThe reaction mixture was then cooled to RT
  4. extractionextracted in DCM
  5. washwashed with water and brine
  6. dry with materialdried over Na2SO4
  7. customto yield a crude solid (0.25 g)
  8. customThe crude product was chromatographed on silica
  9. washeluted with 0-70% Magic Base/DCM
  10. filtrationfiltered
  11. customevaporated

Sources & evidence

ORD record
ord-6d9434ac862747a3bbdd8b2dc78b0e1e
Source dataset
uspto-grants-2012_07
Patent number
US08227478B2

Reaction notes

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