Dichloromethane → HCID 178481827, compound

HRID 1191216Notes

Reaction equation

HRID 1191216 reaction equation
[NH2:1][C:2]1[C:3]([NH:9][C:10]([C:12]2[N:13]([CH3:22])[N:14]=[C:15]([C:18]([CH3:21])([CH3:20])[CH3:19])[C:16]=2[Cl:17])=O)=[N:4][CH:5]=[C:6](Br)[N:7]=1.[F:23][C:24]([F:36])([F:35])[O:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1B(O)O.C([O-])([O-])=O.[Cs+].[Cs+].C(Cl)Cl>O1CCOCC1.CCOC(C)=O.O>[C:18]([C:15]1[C:16]([Cl:17])=[C:12]([C:10]2[NH:9][C:3]3=[N:4][CH:5]=[C:6]([C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=4[O:25][C:24]([F:23])([F:36])[F:35])[N:7]=[C:2]3[N:1]=2)[N:13]([CH3:22])[N:14]=1)([CH3:21])([CH3:20])[CH3:19]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 27772042-(Trifluoromethoxy)phenylboronic Acid (contains varying amounts of Anhydride)HCID 866574135-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid (3-amino-5-bromo-pyrazin-2-yl)-amide

Product 1

HCID 178481827HCID 178481827, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 5-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid (3-amino-5-bromo-pyrazin-2-yl)-amide (45.0 mg, 0.116 mmol, prepared as described in the previous step), 2-trifluoromethoxy-phenyl-boronic acid (28.7 mg, 0.139 mmol), Cs2CO3 (95 mg, 0.29 mmol) and Pd(dppf)2.DCM (9.5 mg, 0.012 mmol) in 1,4-dioxane (3 mL) was added water (1.5 mL). After stirring at 100° C. for 16 h, the resulting mixture was cooled to room temperature and treated with EtOAc (50 mL), washed with H2O (20 mL), brine (20 mL) and then dried with Na2SO4. Removal of the solvent under reduced pressure followed by flash chromatography of the residue on silica gel (0:100-35:65 EtOAc-hexanes) yielded 2-(5-tert-Butyl-4-chloro-2-methyl-2H-pyrazol-3-yl)-5-(2-trifluoromethoxy-phenyl)-1H-imidazo[4,5-b]pyrazine as a light yellow solid. 1H-NMR (400 MHz, CD3OD) δ: 8.79 (s, 1H), 7.87-7.94 (m, 1H), 7.45-7.64 (m, 3H), 4.14 (s, 3H), 1.44 (s, 9H). Mass Spectrum (LCMS, ESI pos.) Calculated For C20H18ClF3N6O: 451.1 (M+H), Measured: 451.1.

Workup

  1. customprepared
  2. temperaturethe resulting mixture was cooled to room temperature
  3. washwashed with H2O (20 mL), brine (20 mL)
  4. dry with materialdried with Na2SO4
  5. customRemoval of the solvent under reduced pressure

Sources & evidence

ORD record
ord-23567445799a413bb7c94a553f434dcd
Source dataset
uspto-grants-2014_03
Patent number
US08680098B2

Reaction notes

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