Glycolic Acid → N-[(2R)-2-({4-[3-chloro-4-hydroxyanilino]quinazolin-5-yl}oxy)propyl]-2-hydroxy-N-methylacetamide
Reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][C:17]=3[O:19][C@H:20]([CH3:24])[CH2:21][NH:22][CH3:23])[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:4][C:3]=1[OH:25].[C:26]([OH:30])(=O)[CH2:27][OH:28].OCC(N(CCOC1C=CC=C2C=1C(NC1C=CC(O)=C(C)C=1)=NC=N2)C)=O>>[Cl:1][C:2]1[CH:7]=[C:6]([CH:5]=[CH:4][C:3]=1[OH:25])[NH:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][C:17]=2[O:19][C@H:20]([CH3:24])[CH2:21][N:22]([CH3:23])[C:26](=[O:30])[CH2:27][OH:28])[N:12]=[CH:11][N:10]=1Participants
Reactant 3
Product 1
Procedure
The N-[(2R)-2-({4-[(3-chloro-4-hydroxyphenyl)amino]quinazolin-5-yl}oxy)propyl]-2-hydroxy-N-methylacetamide starting material was prepared by reacting 2-chloro-4-({5-[(1R)-1-methyl-2-(methylamino)ethoxy]quinazolin-4-yl}amino)phenol with and glycolic acid using an analogous procedure to that described in Example 3 for the preparation of 2-hydroxy-N-[2-({4-[4-hydroxy-3-methylanilino]quinazolin-5-yl}oxy)ethyl]-N-methylacetamide, to give N-[(2R)-2-({4-[3-chloro-4-hydroxyanilino]quinazolin-5-yl}oxy)propyl]-2-hydroxy-N-methylacetamide in 57% yield; NMR spectrum (DMSO-d6) 1.39 (d, 3H), 2.91 (m, 1H), 2.97 (s, 3H), 3.39 (dd, 1H), 4.04 (d, 2H), 4.16 (m, 1H), 4.39 (m, 1H), 5.08 (m, 1H), 6.98 (d, 1H), 7.27 (m, 2H), 7.47 (dd, 1H), 7.70 (t, 1H), 7.97 (d, 1H), 8.43 (s, 1H), 9.85 (s, 1H), 9.99 (bs, 1H); Mass spectrum MH+ 417.
Workup
- customThe N-[(2R)-2-({4-[(3-chloro-4-hydroxyphenyl)amino]quinazolin-5-yl}oxy)propyl]-2-hydroxy-N-methylacetamide starting material was prepared
Sources & evidence
- ORD record
- ord-94d9da36053243c5bf348e6502cfb53a
- Source dataset
- uspto-grants-2009_12
- Patent number
- US07625908B2
Reaction notes
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