Diethylamine → 4-[6-(3-Diethylamino-prop-1-ynyl)-quinazolin-4-yl]-piperidine-1-carboxylic acid (4-isopropoxy-phenyl)-amide

HRID 657204Notes

Reaction equation

HRID 657204 reaction equation
[CH:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]([N:14]2[CH2:19][CH2:18][CH:17]([C:20]3[C:29]4[C:24](=[CH:25][CH:26]=[C:27]([C:30]#[C:31][CH2:32]OS(C)(=O)=O)[CH:28]=4)[N:23]=[CH:22][N:21]=3)[CH2:16][CH2:15]2)=[O:13])=[CH:7][CH:6]=1)([CH3:3])[CH3:2].[CH2:38]([NH:40][CH2:41][CH3:42])[CH3:39]>CC#N>[CH:1]([O:4][C:5]1[CH:6]=[CH:7][C:8]([NH:11][C:12]([N:14]2[CH2:19][CH2:18][CH:17]([C:20]3[C:29]4[C:24](=[CH:25][CH:26]=[C:27]([C:30]#[C:31][CH2:32][N:40]([CH2:41][CH3:42])[CH2:38][CH3:39])[CH:28]=4)[N:23]=[CH:22][N:21]=3)[CH2:16][CH2:15]2)=[O:13])=[CH:9][CH:10]=1)([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 8021DiethylamineHCID 58770853Methanesulfonic acid 3-{4-[1-(4-isopropoxy-phenylcarbamoyl)-piperidin-4-yl]-quinazolin-6-yl}-prop-2-ynyl ester

Product 1

HCID 587706724-[6-(3-Diethylamino-prop-1-ynyl)-quinazolin-4-yl]-piperidine-1-carboxylic acid (4-isopropoxy-phenyl)-amideYield 79%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of methanesulfonic acid 3-{4-[1-(4-isopropoxy-phenylcarbamoyl)-piperidin-4-yl]-quinazolin-6-yl}-prop-2-ynyl ester (180.0 mg, 345 μmol), as prepared in the previous step, in CH3CN (0.5 mL) was treated with diethylamine (79 μL, 759 μmol) very rapidly by syringe in 1 portion with stirring at rt, and the pale yellow solution was allowed to stir at rt for 2 h. Purification of the crude reaction with a flash silica column (1:2 hex/acetone) afforded the title compound as an off-white foam (136 mg, 79%). 1H-NMR (300 MHz, CDCl3) δ 9.22 (s, 1H), 8.21 (d, 1H), 7.99 (d, 1H), 7.88 (dd, 1H), 7.25 (m, 2H), 6.84 (m, 2H), 6.38 (br s, 1H), 4.48 (heptet, 1H), 4.32-4.22 (m, 2H), 3.78-3.65 (m, 1H), 3.70 (s, 2H), 3.16 (td, 2H), 2.68 (q, 4H), 2.21-1.94 (m, 4H), 1.31 (d, 6H), 1.15 (t, 6H). LC/MS (ESI): calcd mass 499.3, found 500.5 (MH)+. A select fraction of this material was submitted for combustion analysis: Anal. Calcd for C30H37N5O2.0.18 water: C, 71.65; H, 7.49; N, 13.93. Found: C, 71.7; H, 7.55; N, 13.92.

Workup

  1. stirringto stir at rt for 2 h
  2. customPurification of the crude
  3. customreaction with a flash silica column (1:2 hex/acetone)

Sources & evidence

ORD record
ord-01094f325993401da31a9a4c03cbb672
Source dataset
uspto-grants-2011_12
Patent number
US08071768B2

Reaction notes

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