Dimethylformamide → HCID 178497461, compound

HRID 1861052Notes

Reaction equation

HRID 1861052 reaction equation
I[C:2]1[C:10]2[C:5](=[CH:6][C:7]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][O:19][CH3:20])=[C:13]([O:21][CH3:22])[CH:12]=3)=[CH:8][CH:9]=2)[NH:4][N:3]=1.[Li]C1C=CC=CC=1.[Li]C(CC)C.CN([CH:38]=[O:39])C>C1COCC1>[CH3:22][O:21][C:13]1[CH:12]=[C:11]([C:7]2[CH:6]=[C:5]3[C:10]([C:2]([CH:38]=[O:39])=[N:3][NH:4]3)=[CH:9][CH:8]=2)[CH:16]=[CH:15][C:14]=1[O:17][CH2:18][O:19][CH3:20]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 178418400CID 53628100HCID 178497462HCID 178497462, compoundHCID 178506676HCID 178506676, compound

Product 1

HCID 178497461HCID 178497461, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

In a 100-mL round-bottom flask, 3-iodo-6-(3-methoxy-4-methoxymethoxy-phenyl)-1H-indazole (921 mg, 2.245 mmol, 1.00 equiv) was dissolved in THF (36 mL) and cooled to −78° C. (allow 8 min at this scale). A solution of PhLi (2.5 mL, 1.8M, 4.49 mmol, 2.00 equiv) was added and the mixture was allowed to stir for 30 min. A solution of s-BuLi (3.63 mL, 4.71 mmol, 2.1 equiv) was added and the reaction mixture was allowed to stir for 1 h at −78° C. Neat DMF (1.4 mL, 18 mmol, 8.0 equiv) was added. The cold bath was removed and the reaction was allowed to slowly warm to 0° C. in the air. As the ice melted saturated sodium bicarbonate (20 mL) was added. The product was extracted into ethyl acetate (200 mL) from saturated sodium bicarbonate (75 mL more), dried over sodium sulfate, decanted and concentrated under reduced pressure. Purification by silica gel chromatography (450 mL silica, 4:6 ethyl acetate/hexane) gave 6-(3-methoxy-4-methoxymethoxy-phenyl)-1H-indazole-3-carbaldehyde (498 mg, 71%)): Rf sm 0.30, p 0.14 (ethyl acetate-hexane 4:6); 1H NMR (CDCl3) δ 10.85 (bs, 1H), 10.25 (s, 1H), 8.37 (d, 1H, J=8.4 Hz), 7.67 (s, 1H), 7.60 (d, 1H, J=8.4 Hz), 6.26 (d, 1H, J=8.7 Hz), 7.19 (m, 2H), 5.30 (s, 2H), 3.99 (s, 3H), 3.55 (s, 3H).

Workup

  1. stirringto stir for 1 h at −78° C
  2. customThe cold bath was removed
  3. temperatureto slowly warm to 0° C. in the air
  4. additionAs the ice melted saturated sodium bicarbonate (20 mL) was added
  5. extractionThe product was extracted into ethyl acetate (200 mL) from saturated sodium bicarbonate (75 mL more),
  6. dry with materialdried over sodium sulfate
  7. customdecanted
  8. concentrationconcentrated under reduced pressure
  9. customPurification by silica gel chromatography (450 mL silica, 4:6 ethyl acetate/hexane)

Sources & evidence

ORD record
ord-c9053958539a4a81821742dddb9a754b
Source dataset
uspto-grants-2003_03
Patent number
US06531491B1

Reaction notes

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