Triethylamine → 3-Cyclopentyl-1-(4-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)propan-1-one

HRID 2079281Notes

Reaction equation

HRID 2079281 reaction equation
[CH3:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([N:19]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)=[N:7][C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[OH:18])=[N:9]2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH:32]1([CH2:37][CH2:38][C:39](Cl)=[O:40])[CH2:36][CH2:35][CH2:34][CH2:33]1>C(Cl)Cl>[CH:32]1([CH2:37][CH2:38][C:39]([N:22]2[CH2:23][CH2:24][N:19]([C:6]3[C:5]4[C:10](=[CH:11][C:2]([CH3:1])=[CH:3][CH:4]=4)[N:9]=[C:8]([C:12]4[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=4[OH:18])[N:7]=3)[CH2:20][CH2:21]2)=[O:40])[CH2:36][CH2:35][CH2:34][CH2:33]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 660393-Cyclopentylpropionyl chlorideHCID 1361346166-[7-methyl-4-(1-piperazinyl)-1H-quinazolin-2-ylidene]-1-cyclohexa-2,4-dienone

Product 1

HCID 1361214493-Cyclopentyl-1-(4-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)propan-1-oneYield 87.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-15 °C

Procedure

A solution of 2-(7-methyl-4-(piperazin-1-yl)quinazolin-2-yl)phenol (200 mg, 0.62 mmol) in CH2Cl2 (6.0 mL) was stirred under an N2 atmosphere. Then triethylamine (170 μL, 1.24 mmol) was added, and the reaction was cooled to −10 to −20° C. After adding 3-cyclopentylpropanoyl chloride (96 μL in 600 μL THF, 0.62 mmol), the reaction mixture was stirred for 30 minutes. CH2Cl2 was added, and the organic phase was washed 2× with H2O, dried over Na2SO4, and concentrated. Purification via silica gel chromatography using 0-10% EtOAc in 50:50 CH2Cl2: hexanes gave 3-cyclopentyl-1-(4-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)propan-1-one (240 mg, 86%). LC/MS: m/z 445.50 (M+H)+ at 3.07 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)). 1H NMR (400 MHz, DMSO-d6) d 8.45 (dd, J=8.2, 1.8 Hz, 1H), 8.00 (d, J=8.5 Hz, 1H), 7.69 (s, 1H), 7.39 (m, 2H), 6.95 (m, 2H), 3.95 (dd, J=19.9, 5.6 Hz, 4H), 3.74 (m, 4H), 2.52 (s, 3H), 2.38 (t, J=7.8 Hz, 2H), 1.76 (m, 3H), 1.55 (m, 6H), 1.16 (m, 2H) ppm.

Workup

  1. washthe organic phase was washed 2× with H2O
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. customPurification via silica gel chromatography

Sources & evidence

ORD record
ord-05524a4bbb814c11b083aa369c2e59ca
Source dataset
uspto-grants-2011_04
Patent number
US07928107B2

Reaction notes

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