Toluene → HCID 178434521, compound

HRID 1516444Notes

Reaction equation

HRID 1516444 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:33](B2OC(C)(C)C(C)(C)O2)=[CH:32][NH:31][N:30]=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>[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:33]5[C:29]([CH3:28])=[N:30][NH:31][CH:32]=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

8

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 67426785HCID 67426785, compoundHCID 178434487HCID 178434487, compound2×

Product 1

HCID 178434521HCID 178434521, compoundYield 149.7%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 702EthanolSolvent2×HCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of [4-(4-iodobenzotriazol-1-yl)-pyrimidin-2-yl]-(1-methanesulfonyl-piperidin-4-yl)-amine (250 mg), 3-methyl-pyrazole-4-boronic acid pinacol ester (109 mg) and Na2CO3 (2 M aq, 0.7 mL, degassed), toluene (9 mL, degassed) and EtOH (0.7 mL) was added to a screw cap pressure flask. 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, and additional portions of 3-methyl-pyrazole-4-boronic acid pinacol ester (109 mg), Pd(PPh3)4 (20 mg), and EtOH (5 mL) added. The flask was again sealed and heated 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 (0.34 g). The solid was chromatographed on silica, eluting with 0-60% Magic Base/DCM, then chromatographed again on silica using 0-60% Magic Base/DCM. The product was titurated with Et2O, filtered, and dried in vacuo overnight to provide (1-methanesulfonyl-piperidin-4-yl)-{4-[4-(3-methyl-1H-pyrazol-4-yl)-benzotriazol-1-yl]-pyrimidin-2-yl}-amine (Compound 10, 39 mg). Mp=231-232° C.; M+H=454.

Workup

  1. additionwas added to a screw
  2. customcap pressure flask
  3. customthe flask sealed
  4. temperatureThe reaction mixture was then cooled to RT
  5. customThe flask was again sealed
  6. temperatureheated overnight at 110° C
  7. extractionextracted in DCM
  8. washwashed with water and brine
  9. dry with materialdried over Na2SO4

Sources & evidence

ORD record
ord-e25d8df1fcf44b7f9ddb9d0757cb4fc5
Source dataset
uspto-grants-2012_07
Patent number
US08227478B2

Reaction notes

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