Pyrazole → HCID 86681127, compound

HRID 1848157Notes

Reaction equation

HRID 1848157 reaction equation
C([O-])([O-])=O.[K+].[K+].[NH:7]1[CH:11]=[CH:10][CH:9]=[N:8]1.I[C:13]1[CH:14]=[C:15]2[N:21]=[CH:20][N:19]([CH2:22][C:23]3[CH:39]=[CH:38][C:26]4[N:27]=[C:28]([NH:30][C@@H:31]5[CH2:36][CH2:35][CH2:34][CH2:33][C@H:32]5[OH:37])[S:29][C:25]=4[CH:24]=3)[C:16]2=[N:17][CH:18]=1.CN[C@@H]1CCCC[C@H]1NC>CN(C=O)C.CO.[Cu]I>[N:7]1([C:13]2[CH:14]=[C:15]3[N:21]=[CH:20][N:19]([CH2:22][C:23]4[CH:39]=[CH:38][C:26]5[N:27]=[C:28]([NH:30][C@@H:31]6[CH2:36][CH2:35][CH2:34][CH2:33][C@H:32]6[OH:37])[S:29][C:25]=5[CH:24]=4)[C:16]3=[N:17][CH:18]=2)[CH:11]=[CH:10][CH:9]=[N:8]1

Participants

8

Reactant 4

HCID 1048PyrazoleHCID 11430Potassium CarbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 86681061HCID 86681061, compound

Product 1

HCID 86681127HCID 86681127, compoundYield 64%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

To a stirred solution of CuI (14 mg, 0.0053 mmol), K2CO3 (102 mg, 0.74 mmol), and pyrazole (30 mg, 0.44 mmol) in 2 mL of DMF under argon was added (1R,2R)-2-((6-((6-iodo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol from Step 2 of Example 96 (150 mg, 0.30 mmol) and trans-N1,N2-dimethylcyclohexane-1,2-diamine (21 mg, 0.15 mmol). The reaction mixture was then heated at 110° C. overnight. The mixture was cooled to rt, diluted with MeOH, and purified by preparative HPLC using a mixture of water (5% CH3CN, 0.05% AcOH) and CH3CN (0.05% AcOH) as the mobile phase and Varian Pursuit XRs Diphenyl column as the stationary phase to afford (1R,2R)-2-((6-((6-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (85 mg, 64%) as a white solid. 1H NMR (500 MHz, DMSO-d6) δ 8.92 (d, J=2.0 Hz, 1H), 8.69 (s, 1H), 8.57 (d, J=2.5 Hz, 1H), 8.50 (d, J=2.5 Hz, 1H), 7.96 (d, J=7.4 Hz, 1H), 7.79 (s, 1H), 7.68 (s, 1H), 7.29 (s, 1H), 7.20-7.27 (m, 1H), 6.58 (s, 1H), 5.52 (s, 2H), 4.74 (br s, 1H), 3.51 (br s, 1H), 2.03 (d, J=12.3 Hz, 1H), 1.80-1.95 (m, 1H), 1.52-1.72 (m, 2H), 1.08-1.33 (m, 4H). LCMS (ESI) m/z 446 (M+H)+.

Workup

  1. temperatureThe mixture was cooled to rt
  2. custompurified by preparative HPLC
  3. additiona mixture of water (5% CH3CN, 0.05% AcOH) and CH3CN (0.05% AcOH) as the mobile phase and Varian Pursuit XRs Diphenyl column as the stationary phase

Sources & evidence

ORD record
ord-fcdc5e7be8614a2fa3a28cfaf471621e
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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