3-Fluoroaniline → 2-[3-({5-{[1-(2-tert-butoxyethyl)piperidin-4-yl]oxy}-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazolin-4-yl}amino)-1H-pyrazol-5-yl]-N-(3-fluorophenyl)acetamide

HRID 749183Notes

Reaction equation

HRID 749183 reaction equation
[C:1]([O:5][CH2:6][CH2:7][N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:24]=[C:23]([O:25][CH2:26][CH2:27][CH2:28][N:29]3[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]3)[CH:22]=[C:21]3[C:16]=2[C:17]([NH:36][C:37]2[CH:41]=[C:40]([CH2:42][C:43]([OH:45])=O)[NH:39][N:38]=2)=[N:18][CH:19]=[N:20]3)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[F:46][C:47]1[CH:48]=[C:49]([CH:51]=[CH:52][CH:53]=1)[NH2:50].Cl.CN(C)CCCN=C=NCC.OC1C=CC=C[N+]=1[O-]>CN(C)C=O.ClCCl>[NH3:8].[C:1]([O:5][CH2:6][CH2:7][N:8]1[CH2:9][CH2:10][CH:11]([O:14][C:15]2[CH:24]=[C:23]([O:25][CH2:26][CH2:27][CH2:28][N:29]3[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]3)[CH:22]=[C:21]3[C:16]=2[C:17]([NH:36][C:37]2[CH:41]=[C:40]([CH2:42][C:43]([NH:50][C:49]4[CH:51]=[CH:52][CH:53]=[C:47]([F:46])[CH:48]=4)=[O:45])[NH:39][N:38]=2)=[N:18][CH:19]=[N:20]3)[CH2:12][CH2:13]1)([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 4

HCID 97423-FluoroanilineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68988732[3-({5-{[1-(2-tert-butoxyethyl)piperidin-4-yl]oxy}-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazolin-4-yl}amino)-1H-pyrazol-5-yl]acetic acidHCID 178526252HCID 178526252, compound

Product 2

HCID 222AmmoniaHCID 689932112-[3-({5-{[1-(2-tert-butoxyethyl)piperidin-4-yl]oxy}-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazolin-4-yl}amino)-1H-pyrazol-5-yl]-N-(3-fluorophenyl)acetamideYield 138%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

[3-({5-{[1-(2-tert-butoxyethyl)piperidin-4-yl]oxy}-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazolin-4-yl}amino)-1H-pyrazol-5-yl]acetic acid (140 mg, 0.22 mmol) in dimethylformamide (1 ml) was reacted with 3-fluoroaniline (24 μl, 0.25 mmol) in the presence of 1-(3-dimethylamino-propyl)-3-ethylcarbodiimide hydrochloride (48 mg, 0.25 mmol) and 2-hydroxypyridin-1-oxide (27 mg, 0.24 mmol) at 50° C. for 45 minutes. The solvent was evaporated and the residue purified by chromatography on silica gel. Elution with dichloromethane:methanol (97:3) then dichloromethane:methanolic ammonia (95:5) yielded 2-[3-({5-{[1-(2-tert-butoxyethyl)piperidin-4-yl]oxy}-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazolin-4-yl}amino)-1H-pyrazol-5-yl]-N-(3-fluorophenyl)acetamide (109 mg, 58% yield):

Workup

  1. customThe solvent was evaporated
  2. customthe residue purified by chromatography on silica gel
  3. washElution with dichloromethane:methanol (97:3)

Sources & evidence

ORD record
ord-0d0fdc3518e2425ca07a49e3e8e96b86
Source dataset
uspto-grants-2008_07
Patent number
US07402585B2

Reaction notes

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