Toluene → HCID 46833493, compound

HRID 1516435Notes

Reaction equation

HRID 1516435 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.[CH3:33][C:34]1[C:35](B(O)O)=[CH:36][S:37][CH:38]=1.[C:42]([O-])([O-])=[O:43].[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>[NH4+:5].[OH-:1].[CH3:42][OH:43].[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[C:34]([CH3:33])=[CH:38][S:37][CH:36]=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

9

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 50839314-Methyl-3-thiopheneboronic acidHCID 67425529HCID 67425529, compound

Product 2

HCID 21894508Ammonium hydroxide methanolYield 1%HCID 46833493HCID 46833493, compoundYield 40%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

A mixture of (4-hydroxy-piperidin-1-yl)-{4-[4-(4-iodobenzotriazol-1-yl)-pyrimidin-2-ylamino]-cyclohexyl}-methanone (0.25 g), 4-methyl-3-thiopheneboronic acid (0.068 g) and Na2CO3 (2 M, 0.7 mL, degassed) was stirred at RT under N2 for 15 min. To this was added Pd(PPh3)4 (0.016 g) with toluene (8 mL, degassed) and EtOH (0.5 mL), and the mixture stirred overnight at 110° C. The reaction mixture was then 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 flash-chromatographed on silica, eluting with DCM: 1% NH4OH-MeOH (1000:50) to provide (4-hydroxy-piperidin-1-yl)-(4-{-4-[4-(4-methylthiophen-3-yl)-benzotriazol-1-yl]-pyrimidin-2-yl-amino}-cyclohexyl)-methanone (Compound 1, 0.114 g, 40%) as an off-white solid. Mp=246-247° C.; M+H=518.

Workup

  1. stirringthe mixture stirred overnight at 110° C
  2. extractionextracted in DCM
  3. washwashed with water and brine
  4. dry with materialdried over Na2SO4
  5. customto yield a solid
  6. customThe solid was flash-chromatographed on silica
  7. washeluting with DCM

Sources & evidence

ORD record
ord-33ebf6e1ac1e40ffac2aee484cbcdffe
Source dataset
uspto-grants-2012_07
Patent number
US08227478B2

Reaction notes

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