1,2-Dichloroethane → HCID 135486190, compound

HRID 2211944Notes

Reaction equation

HRID 2211944 reaction equation
C(OC([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17](O)=[O:18])=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:20]1[C:28]2[C:23](=[CH:24][C:25](Cl)=[CH:26][CH:27]=2)[NH:22][N:21]=1)=O)(C)(C)C.[CH3:30][N:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.C(N(CC)CC)C>CN(C=O)C>[CH3:30][N:31]1[CH2:36][CH2:35][N:34]([C:17]([C:13]2[CH:12]=[C:11]3[C:16](=[CH:15][CH:14]=2)[NH:8][C:9]([C:20]2[C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[NH:22][N:21]=2)=[CH:10]3)=[O:18])[CH2:33][CH2:32]1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 531671-MethylpiperazineHCID 181649HOAtHCID 21048654HCID 21048654, compound

Product 1

HCID 135486190HCID 135486190, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 1-(tert-butoxycarbonyl)-2-(1H-indazol-3-yl)-1H-indole-5-carboxylic acid (4-5, 100 mg, 0.265 mmol), N-methyl piperazine (40 μL, 0.32 mmol), EDC (61 mg, 0.32 mmol), and HOAt (43.3 mg, 0.32 mmol)in 5 ml of DMF was treated with triethylamine (90 μL, 0.66 mmol) and mixed for 24 h. The solution was partitioned between ethyl acetate (3×50 mL) and water (75 mL). The combined organics were dried over Na2SO4, filtered and concentrated. The residual oil was dissolved in a 1:1 mixture of dichloromethane/trifluoroacetic acid and mixed for 45 min. The solvent was removed in vacuo and the residue was purified by reverse phase liquid chromatography (H2O/CH3CN gradient with 0.1% 1TFA present) to provide 3-{5-[(4-methylpiperazin-1-yl)carbonyl]-1H-indol-2-yl}-1H-indazole (4-6); 1H NMR (500 MHz, CD3OD) δ 11.36 (s, 1H), 8.14 (d, 1H, J=8.3 Hz), 7.83 (s, 1H), 7.58 (dd, 2H, J=8.5 Hz), 7.45 (t, 1H, J=8.3 Hz), 7.30 (dd, 2H, J=8.06 Hz), 7.17 (s, 1H), 4.55 (bs, 2H), 3.45 (bs, 2H), 3.25 (bs, 2H), 2.98 (s, 3H).

Workup

  1. additionmixed for 24 h
  2. customThe solution was partitioned between ethyl acetate (3×50 mL) and water (75 mL)
  3. dry with materialThe combined organics were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe residual oil was dissolved in a 1:1 mixture of dichloromethane/trifluoroacetic acid
  7. additionmixed for 45 min
  8. customThe solvent was removed in vacuo
  9. customthe residue was purified by reverse phase liquid chromatography (H2O/CH3CN gradient with 0.1% 1TFA present)

Sources & evidence

ORD record
ord-8edc0d1ad35449f6aec8d0f34be55cdb
Source dataset
uspto-grants-2006_09
Patent number
US07101884B2

Reaction notes

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