5-Chloro-2-fluoro-4-hydroxybenzaldehyde → 2-Chloro-5-fluoro-4-(6-fluoro-11-methyl-2,3-dihydro-9H-[1,4]dioxino[2,3-f]pyrazolo[3,4-c]isoquinolin-7-yl)phenol

HRID 253299Notes

Reaction equation

HRID 253299 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:12]2[C:13]([CH3:18])=[N:14][NH:15][C:16]=2[NH2:17])[C:5]2[O:10][CH2:9][CH2:8][O:7][C:6]=2[CH:11]=1.[Cl:19][C:20]1[C:21]([OH:29])=[CH:22][C:23]([F:28])=[C:24]([CH:27]=1)[CH:25]=O>FC(F)(F)C(O)=O>[Cl:19][C:20]1[CH:27]=[C:24]([C:25]2[C:3]3[C:4](=[C:5]4[O:10][CH2:9][CH2:8][O:7][C:6]4=[CH:11][C:2]=3[F:1])[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 1784346374-(7-fluoro-2,3-dihydro-1,4-benzodioxin-5-yl)-3-methyl-1H-pyrazol-5-amine

Product 1

HCID 1784343782-Chloro-5-fluoro-4-(6-fluoro-11-methyl-2,3-dihydro-9H-[1,4]dioxino[2,3-f]pyrazolo[3,4-c]isoquinolin-7-yl)phenolYield 4.2%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of 4-(7-fluoro-2,3-dihydro-1,4-benzodioxin-5-yl)-3-methyl-1H-pyrazol-5-amine (109 mg, 0.338 mmol) and 5-chloro-2-fluoro-4-hydroxybenzaldehyde (60 mg, 0.338 mmol) in trifluoroacetic acid (2.0 mL) was heated to 75° C. and allowed to stir for 12 h. The reaction mixture was concentrated in vacuo and the residue was purified by reverse phase HPLC to afford 5.8 mg (4.2%) of 2-Chloro-5-fluoro-4-(6-fluoro-11-methyl-2,3-dihydro-9H-[1,4]dioxino[2,3-f]pyrazolo[3,4-c]isoquinolin-7-yl)phenol as a white powder: 1H NMR (400 MHz, d4-MeOH): 7.67 (d, J=7.6 Hz, 1H), 7.07 (d, J=13.2 Hz, 1H), 6.85 (d, J=10.8 Hz, 1H) 4.59-4.56 (m, 4H), 2.99 (s, 3H); MS (EI) for C19H12ClF2N3O3: 404 (MH+).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-e65d7d42a511459c8cdf2a2e4ff6b1db
Source dataset
uspto-grants-2011_01
Patent number
US07872014B2

Reaction notes

Loading…