Bromobenzene → 2-(4-(1-(4-methoxybenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenylamino)-N-(4-fluorophenyl)nicotinamide

HRID 2241395Notes

Reaction equation

HRID 2241395 reaction equation
[CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16](Cl)=[C:11]3[C:10]([I:18])=[N:9]2)=[CH:5][CH:4]=1.[F:21][C:22]1[CH:23]=[C:24]([NH:29][C:30]2[N:45]=[CH:44][CH:43]=[CH:42][C:31]=2[C:32]([NH:34][C:35]2[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=2)=[O:33])[CH:25]=[CH:26][C:27]=1[OH:28].C(=O)([O-])[O-].[Cs+].[Cs+].BrC1C=CC=CC=1>>[CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:28][C:27]4[CH:26]=[CH:25][C:24]([NH:29][C:30]5[N:45]=[CH:44][CH:43]=[CH:42][C:31]=5[C:32]([NH:34][C:35]5[CH:36]=[CH:37][C:38]([F:41])=[CH:39][CH:40]=5)=[O:33])=[CH:23][C:22]=4[F:21])=[C:11]3[C:10]([I:18])=[N:9]2)=[CH:5][CH:4]=1

Participants

5

Reactant 4

HCID 7961BromobenzeneHCID 10796Cesium carbonateHCID 672207314-chloro-3-iodo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridineHCID 672218842-(3-fluoro-4-hydroxyphenylamino)-N-(4-fluorophenyl)nicotinamide

Product 1

HCID 672218582-(4-(1-(4-methoxybenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenylamino)-N-(4-fluorophenyl)nicotinamideYield 79.4%

Conditions

Temperature
160 °C

Procedure

A 100 mL sealable tube was charged with 1-(4-methoxybenzyl)-4-chloro-3-iodo-1H-pyrazolo[3,4-b]pyridine (0.250 g, 0.626 mmol Example 84, Step D), 2-(3-fluoro-4-hydroxyphenylamino)-N-(4-fluorophenyl)nicotinamide (0.427 g, 1.25 mmol), cesium carbonate (0.408 g, 1.25 mmol), and 1-bromobenzene (6.26 ml, 0.626 mmol). The reaction mixture was heated to 160° C. for 18 hours. The reaction mixture was cooled to ambient temperature and concentrated. The residue was dissolved in EtOAc and washed with brine. The crude material was purified by silica gel (Biotage 40S) eluting with 4:1 Hexane/EtOAc to provide the product (0.35 g, 71%). LRMS M−1 (704.9) observed.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. concentrationconcentrated
  3. dissolutionThe residue was dissolved in EtOAc
  4. washwashed with brine
  5. customThe crude material was purified by silica gel (Biotage 40S)
  6. washeluting with 4:1 Hexane/EtOAc

Sources & evidence

ORD record
ord-9d86c0bdc34045ef93743a69daa3cde7
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

Loading…