Tetrahydro-2-furoic acid, (+)- → (4-{4-[6,7-Bis-(2-methoxy-ethoxy)-quinazolin-4-ylamino]-2-methyl-phenoxy}-piperidin-1-yl)-(tetrahydro-furan-2-yl)-methanone

HRID 731903Notes

Reaction equation

HRID 731903 reaction equation
[O:1]1[CH2:5][CH2:4][CH2:3][C@@H:2]1[C:6]([OH:8])=O.Cl.[CH3:10][O:11][CH2:12][CH2:13][O:14][C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][C:24]=1[O:25][CH2:26][CH2:27][O:28][CH3:29])[N:21]=[CH:20][N:19]=[C:18]2[NH:30][C:31]1[CH:36]=[CH:35][C:34]([O:37][CH:38]2[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]2)=[C:33]([CH3:44])[CH:32]=1>CN(C)C=O>[CH3:10][O:11][CH2:12][CH2:13][O:14][C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][C:24]=1[O:25][CH2:26][CH2:27][O:28][CH3:29])[N:21]=[CH:20][N:19]=[C:18]2[NH:30][C:31]1[CH:36]=[CH:35][C:34]([O:37][CH:38]2[CH2:39][CH2:40][N:41]([C:6]([CH:2]3[CH2:3][CH2:4][CH2:5][O:1]3)=[O:8])[CH2:42][CH2:43]2)=[C:33]([CH3:44])[CH:32]=1

Participants

4

Reactant 2

HCID 2734707Tetrahydro-2-furoic acid, (+)-HCID 69051900[6,7-Bis-(2-methoxy-ethoxy)-quinazolin-4-yl]-[3-methyl-4-(piperidin-4-yloxy)-phenyl]-amine hydrochloride

Product 1

HCID 69054165(4-{4-[6,7-Bis-(2-methoxy-ethoxy)-quinazolin-4-ylamino]-2-methyl-phenoxy}-piperidin-1-yl)-(tetrahydro-furan-2-yl)-methanone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1,1′-carbonyldiimidizole (35 mg, 0.221 mmol) in N,N-dimethylformamide (2 mL) was added (R)-(+)-tetrahydrofuroic acid (25 mg, 0.221 mmol). The reaction was stirred at room temperature for 30 minutes then [6,7-Bis-(2-methoxy-ethoxy)-quinazolin-4-yl]-[3-methyl-4-(piperidin-4-yloxy)-phenyl]-amine hydrochloride (100 mg, 0.193 mmol) was added. The reaction was then stirred at room temperature overnight. The following day, the reaction was filtered through a 0.45 μm PTFE membrane filter and purified by preparatory HPLC. 1H NMR (300 MHz, DMSO-d6) δ 9.38(bs, 1H), 8.39(s, 1H), 8.15(s, 1H), 7.85(s, 1H), 7.52(d, J=8.39 Hz, 1H), 7.19(s, 1H), 7.04(d, J=8.71 Hz, 1H), 4.70(t, J=7.46, 1.55 Hz, 1H), 4.64(t, J=18.66, 3.42 Hz, 1H), 4.84(t, J=4.97, 3.75 Hz, 2H), 3.77(m, 8H), 3.43(m, 2H), 3.38(s, 3H), 3.36(s, 3H), 2.21(s, 3H), 2.05(m, 4H), 1.90(m, 2H), 1.66(m, 2H), LRMS (M+): 581.1, (M−): 579.2.

Workup

  1. stirringThe reaction was then stirred at room temperature overnight
  2. filtrationThe following day, the reaction was filtered through a 0.45 μm PTFE membrane
  3. filtrationfilter
  4. custompurified by preparatory HPLC

Sources & evidence

ORD record
ord-01baafe07eb440dd8c8101ea34e75734
Source dataset
uspto-grants-2009_09
Patent number
US07585869B2

Reaction notes

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