Boron tribromide → 6-hydroxy-1-(5-isopropyl-1H-indazol-4-yl)-3-methyl-isoquinoline-4-carbaldehyde

HRID 606314Notes

Reaction equation

HRID 606314 reaction equation
B(Br)(Br)Br.[CH:5]([C:8]1[C:9]([C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:27]C)=[CH:24][CH:25]=3)[C:20]([CH:29]=[O:30])=[C:19]([CH3:31])[N:18]=2)=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][N:12]=[CH:11]2)([CH3:7])[CH3:6]>C(Cl)Cl>[OH:27][C:23]1[CH:22]=[C:21]2[C:26](=[CH:25][CH:24]=1)[C:17]([C:9]1[C:8]([CH:5]([CH3:7])[CH3:6])=[CH:16][CH:15]=[C:14]3[C:10]=1[CH:11]=[N:12][NH:13]3)=[N:18][C:19]([CH3:31])=[C:20]2[CH:29]=[O:30]

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 866159341-(5-isopropyl-1H-indazol-4-yl)-6-methoxy-3-methyl-isoquinoline-4-carbaldehyde

Product 1

HCID 1363416606-hydroxy-1-(5-isopropyl-1H-indazol-4-yl)-3-methyl-isoquinoline-4-carbaldehydeYield 34.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

BBr3 (8.8 g, 35 mmol) is added slowly to a solution of 1-(5-Isopropyl-1H-indazol-4-yl)-6-methoxy-3-methyl-isoquinoline-4-carbaldehyde (842 mg, 2.3 mmol) in DCM (15 ml) at −78° C. The cold bath is removed and the mixture is warmed to room temperature, and then stirred for a further 1 h. The reaction mixture is poured into ice-water mixture and treated with NH4OH (6 ml). The layers are separated and the aqueous layer is extracted with DCM. The combined organic layers are dried (Na2SO4) and evaporated. The residue is chromatographed on silica gel eluting with EtOAc/MeOH (20:1) to give 490 mg of starting material and 276 mg of 6-hydroxy-1-(5-isopropyl-1H-indazol-4-yl)-3-methyl-isoquinoline-4-carbaldehyde. 1H NMR (CDCl3) 10.9 (s, 1H), 8.87 (s, 1H), 7.62-7.42 (m, 4H), 6.99 (d, 1H), 3.09 (s, 3H), 2.73-2.67 (m, 1H), 1.23 (d, 3H), 1.12 (d, 3H).

Workup

  1. customThe cold bath is removed
  2. additionThe reaction mixture is poured into ice-water mixture
  3. additiontreated with NH4OH (6 ml)
  4. customThe layers are separated
  5. extractionthe aqueous layer is extracted with DCM
  6. dry with materialThe combined organic layers are dried (Na2SO4)
  7. customevaporated
  8. customThe residue is chromatographed on silica gel eluting with EtOAc/MeOH (20:1)

Sources & evidence

ORD record
ord-87572e2fb1c248c6a992207cef683825
Source dataset
uspto-grants-2011_03
Patent number
US07915288B2

Reaction notes

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