Iodine → HCID 178461646, compound

HRID 69239Notes

Reaction equation

HRID 69239 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[CH:9][C:10]3[N:11]([C:13]([C:16]([C:19]4[CH:27]=[CH:26][C:25]5[C:21](=[CH:22][N:23](COCC[Si](C)(C)C)[N:24]=5)[CH:20]=4)(O)[CH3:17])=[CH:14][N:15]=3)[N:12]=2)[CH:4]=[N:3]1.II.O[PH2]=O>C(O)(=O)C>[N:24]1[NH:23][CH:22]=[C:21]2[C:25]=1[CH:26]=[CH:27][C:19]([C@@H:16]([C:13]1[N:11]3[N:12]=[C:7]([C:5]4[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=4)[CH:8]=[CH:9][C:10]3=[N:15][CH:14]=1)[CH3:17])=[CH:20]2

Participants

5

Reactant 3

HCID 807IodineHCID 4124402Phosphinic AcidHCID 68640428(Rac)-1-[6-(1-methyl-1h-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-yl]-1-[2-(2-trimethylsilanyl-ethoxymethyl)-2h-indazol-5-yl]-ethanol

Product 1

HCID 178461646HCID 178461646, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of (rac)-1-[6-(1-Methyl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-yl]-1-[2-(2-trimethylsilanyl-ethoxymethyl)-2H-indazol-5-yl]-ethanol (Stage 195.1, 194 mg, 0.396 mmol) in acetic acid (2.2 mL) were added iodine (201 mg, 0.792 mmol) and H3PO2 (0.436 mL of a 50% aqueous solution, 3.96 mmol). The mixture was then heated to 150° C. for 30 min. After cooling down to rt, the acetic acid was removed in vacuo and the residue was diluted with water and 10% Na2CO3-solution. The precipitate was filtered and washed with water and dried under vacuum overnight to afford the racemate. The mixture was then separated with a Preparative HPLC on a Chiralpak ADOOSC-JF004 (2.5×20 cm) column with a flow of 80 mL/min of n-heptane:EtOH:MeOH 70:25:10 (v/v). Oven 20° C., detection 210 nm (tR 41.3 min) to afford the title compound as a pure enantiomere (tR 3.64 min (conditions 3), MH+=344, 1H-NMR in DMSO-d6: 12.90 (s, 1H); 8.29 (s, 1H); 8.03-7.95 (m, 3H); 7.71 (s, 1H); 7.66 (s, 1H); 7.44-7.33 (m, 3H); 4.73 (q, 1H); 3.87 (s, 3H); 1.77 (d, 3H)).

Workup

  1. temperatureAfter cooling down to rt
  2. customthe acetic acid was removed in vacuo
  3. additionthe residue was diluted with water and 10% Na2CO3-solution
  4. filtrationThe precipitate was filtered
  5. washwashed with water
  6. customdried under vacuum overnight
  7. customto afford the racemate
  8. customThe mixture was then separated with a Preparative HPLC on a Chiralpak ADOOSC-JF004 (2.5×20 cm) column with a flow of 80 mL/min of n-heptane:EtOH:MeOH 70:25:10 (v/v)

Sources & evidence

ORD record
ord-6ca0ea81703d475f98665692f0447108
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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