Pyridine → N-{3-[methyl-(3-styryl-1H-indazol-6-yl)-amino]-phenyl}-acetamide

HRID 1862117Notes

Reaction equation

HRID 1862117 reaction equation
[CH3:1][N:2]([C:10]1[CH:18]=[C:17]2[C:13]([C:14]([CH:27]=[CH:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[N:15][N:16]2COCC[Si](C)(C)C)=[CH:12][CH:11]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([NH2:9])[CH:4]=1.N1C=CC=CC=1.[CH3:41][C:42](OC(C)=O)=[O:43].C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.CN(C1C=CN=CC=1)C.CCOC(C)=O.C(Cl)Cl.CCOC(C)=O>[CH3:1][N:2]([C:10]1[CH:18]=[C:17]2[C:13]([C:14]([CH:27]=[CH:28][C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)=[N:15][NH:16]2)=[CH:12][CH:11]=1)[C:3]1[CH:4]=[C:5]([NH:9][C:42](=[O:43])[CH3:41])[CH:6]=[CH:7][CH:8]=1

Participants

9

Reactant 4

HCID 1049PyridineHCID 7918Acetic AnhydrideHCID 11430Potassium CarbonateHCID 69369951HCID 69369951, compound

Product 1

HCID 69370837N-{3-[methyl-(3-styryl-1H-indazol-6-yl)-amino]-phenyl}-acetamideYield 22%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 21226138Dichloromethane ethylacetateSolvent

Conditions

Temperature
23 °C

Procedure

N-Methyl-N-{3-styryl-1-[2-(trimethyl-silanyl)-ethoxymethyl]-1H-indazol-6-yl}-benzene-1,3-diamine, prepared in Example 11 (34 mg, 0.041 mmol) was suspended in CH2Cl2 (0.5 mL) at 23° C. under an atmosphere of argon. Pyridine (81 μL, 1.0 mmol), Ac2O (94 μl, 1.0 mmol) and DMAP (cat.) were added. The reaction became homogeneous immediately. After 1 h, TLC analysis (CH2Cl2:EtOAc 4:1) indicated no starting material. The reaction was quenched with saturated NaHCO3(aq) (2 mL) then diluted with EtOAc (15 mL) and the organic phase was washed with brine (3 mL), decanted and concentrated under reduced pressure to an oil. The oil was suspended in MeOH (2 mL) and K2CO3 (83 mg, 0.6 mmol) was added. The resulting mixture was stirred at 23° C. under an atmosphere of argon. After 1 h, the reaction was diluted with EtOAc (15 mL) and the organic phase was washed with brine (3 mL), decanted and concentrated under reduced pressure. The crude material was purified by semi-prep HPLC to give N-{3-[methyl-(3-styryl-1H-indazol-6-yl)-amino]-phenyl}-acetamide (8.4 mg, 22%). 1H NMR (300 MHz, CDCl3) δ 7.86 (d, 1H, J=8.68 Hz), 7.58 (d, 1H, J=7.17 Hz), 7.16-7.45 (m, 7H), 7.15 (d, 1H, J=8.29 Hz), 6.98 (m, 1H), 6.95 (d, 1H, J=1.92 Hz), 6.8 (dd, 1H, J=1.16, 8.05 Hz), 3.37 (s, 3H), 2.14 (s, 3H). LCMS (ESI) [M+H]/z Calc'd 383, Found 383. Anal. Calc'd: C, 75.37; H, 5.80; N, 14.65. Found: C, 73.53; H, 6.01; N, 13.73.

Workup

  1. customThe reaction was quenched with saturated NaHCO3(aq) (2 mL)
  2. additionthen diluted with EtOAc (15 mL)
  3. washthe organic phase was washed with brine (3 mL)
  4. customdecanted
  5. concentrationconcentrated under reduced pressure to an oil
  6. waitAfter 1 h
  7. washthe organic phase was washed with brine (3 mL)
  8. customdecanted
  9. concentrationconcentrated under reduced pressure
  10. customThe crude material was purified by semi-prep HPLC

Sources & evidence

ORD record
ord-fcadf43169a1403a811fd2490189aec1
Source dataset
uspto-grants-2003_03
Patent number
US06534524B1

Reaction notes

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