1,1'-Carbonyldiimidazole → HCID 10046603, compound

HRID 658494Notes

Reaction equation

HRID 658494 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([NH2:11])=[CH:8][CH:9]=2)[CH:4]=[N:3]1.[C:12]([N:19]1[CH:23]=[CH:22]N=C1)(N1C=CN=C1)=[O:13].NC1C=[CH:39][C:28]([O:29][C:30]2[CH:35]=[CH:34][N:33]=[C:32]([C:36](=[O:38])[CH3:37])[CH:31]=2)=[CH:27][CH:26]=1>ClCCCl.C1COCC1>[C:36]([C:32]1[CH:31]=[C:30]([O:29][C:28]2[CH:39]=[CH:22][C:23]([NH:19][C:12]([NH:11][C:7]3[CH:6]=[C:5]4[C:10](=[CH:9][CH:8]=3)[N:2]([CH3:1])[N:3]=[CH:4]4)=[O:13])=[CH:26][CH:27]=2)[CH:35]=[CH:34][N:33]=1)(=[O:38])[CH3:37]

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 27680321-methyl-1H-indazol-5-amineHCID 59772959HCID 59772959, compound

Product 1

HCID 10046603HCID 10046603, compoundYield 74.4%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 1-methyl-5-aminoindazole (48.4 mg, 0.33 mmol) in anhydrous DCE (1.1 mL) and anhydrous THF (1.1 mL) was added 1,1′-carbonyldiimidazole (65.1 mg, 0.39, 1.2 eq), and the reaction mixture was stirred at 65° C. under argon. After 16 h a solution of 1-[4-(4-aminophenoxy)pyridin-2-yl]ethanone (75 mg, 0.33 mmol, 1.0 eq) in anhydrous DCE (3.3 mL) was added at ambient temperature, and the reaction mixture was stirred at 65° C. under argon for 20 h. The reaction mixture was partitioned between EtOAc and water, and the organic layer was washed with water and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. Purification on MPLC (biotage) eluted with 60 to 80% EtOAc/Hex and crystallization from ethyl acetate—hexane afforded 98.2 mg (74.4%) of the title compound as a white solid. 1H-NMR (DMSO-d6) δ 8.79 (s, 1H), 8.68 (s, 1H), 8.58 (d, J=5.7 Hz, 1H), 7.93 (d, J=1.0 Hz, 1H), 7.89 (d, J=1.2 Hz, 1H), 7.58 to 7.53 (m, 3H), 7.35 (dd, J=9.0, 2.1 Hz, 1H), 7.26 (d, J=2.7 Hz, 1H), 7.21 (dd, J=5.4, 2.4 Hz, 1H), 7.13 (d, J=8.7 Hz, 2H), 3.99 (s, 3H), 2.59 (s, 3H); MS LC-MS [M+H]+=4.02, RT=2.41 min; TLC (75% EtOAc/Hex), Rf=0.11.

Workup

  1. stirringthe reaction mixture was stirred at 65° C. under argon for 20 h
  2. customThe reaction mixture was partitioned between EtOAc and water
  3. washthe organic layer was washed with water and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification on MPLC (biotage)
  8. washeluted with 60 to 80% EtOAc/Hex and crystallization from ethyl acetate—hexane

Sources & evidence

ORD record
ord-50d183ee33b645d7a14a90f609d7fdc2
Source dataset
uspto-grants-2011_12
Patent number
US08076488B2

Reaction notes

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