5-Chloro-2-fluoro-4-hydroxybenzaldehyde → 2-chloro-5-fluoro-4-(6-fluoro-1-methyl-8,9-dihydro-3H-[1,4]dioxino[2,3-g]pyrazolo[3,4-c]isoquinolin-5-yl)phenol

HRID 253307Notes

Reaction equation

HRID 253307 reaction equation
[F:1][C:2]1[C:7]2[O:8][CH2:9][CH2:10][O:11][C:6]=2[CH:5]=[C:4]([C:12]2[C:13]([CH3:18])=[N:14][NH:15][C:16]=2[NH2:17])[CH:3]=1.[Cl:19][C:20]1[C:21]([OH:29])=[CH:22][C:23]([F:28])=[C:24]([CH:27]=1)[CH:25]=O>C(O)(C(F)(F)F)=O>[Cl:19][C:20]1[CH:27]=[C:24]([C:25]2[C:3]3[C:2]([F:1])=[C:7]4[O:8][CH2:9][CH2:10][O:11][C:6]4=[CH:5][C:4]=3[C:12]3[C:13]([CH3:18])=[N:14][NH:15][C:16]=3[N:17]=2)[C:23]([F:28])=[CH:22][C:21]=1[OH:29]

Participants

4

Reactant 2

HCID 225582325-Chloro-2-fluoro-4-hydroxybenzaldehydeHCID 178434636HCID 178434636, compound

Product 1

HCID 1784343772-chloro-5-fluoro-4-(6-fluoro-1-methyl-8,9-dihydro-3H-[1,4]dioxino[2,3-g]pyrazolo[3,4-c]isoquinolin-5-yl)phenolYield 11.1%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of 4-(8-fluoro-2,3-dihydro-1,4-benzodioxin-6-yl)-3-methyl-1H-pyrazol-5-amine (100 mg, 0.40 mmol) and 5-chloro-2-fluoro-4-hydroxybenzaldehyde (70 mg, 0.40 mmol) in TFA (2 mL) was stirred at 90° C. for 16 h. The reaction mixture was concentrated and purified by preparative reverse phase HPLC to give 2-chloro-5-fluoro-4-(6-fluoro-1-methyl-8,9-dihydro-3H-[1,4]dioxino[2,3-g]pyrazolo[3,4-c]isoquinolin-5-yl)phenol (18 mg, 11% yield) as a yellow solid after lyophillization of the pure fractions. 1H NMR (400 MHz, d6-DMSO) δ 10.98 (s, 1H), 7.55 (m, 2H), 6.86 (dd, 1H), 4.44 (m, 4H), 2.74 (s, 3H); MS (EI) for C19H12ClF2N3O3: 404 (MH+).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. custompurified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-89c84c16752e46c59fb34f8ed14a7415
Source dataset
uspto-grants-2011_01
Patent number
US07872014B2

Reaction notes

Loading…