2-(Methylamino)ethanol → (2R)-2-[(4-{[1-(3-fluorobenzyl)-1H-indazol-5-yl]amino}quinazolin-5-yl)oxy]-N-(2-hydroxyethyl)-N-methylpropanamide
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:33]=[CH:34][CH:35]=1)[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][C:11]([NH:15][C:16]3[C:25]4[C:20](=[CH:21][CH:22]=[CH:23][C:24]=4[O:26][C@H:27]([CH3:32])[C:28](OC)=[O:29])[N:19]=[CH:18][N:17]=3)=[CH:12][CH:13]=2)[CH:8]=[N:7]1.[CH3:36][NH:37][CH2:38][CH2:39][OH:40]>>[F:1][C:2]1[CH:3]=[C:4]([CH:33]=[CH:34][CH:35]=1)[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][C:11]([NH:15][C:16]3[C:25]4[C:20](=[CH:21][CH:22]=[CH:23][C:24]=4[O:26][C@H:27]([CH3:32])[C:28]([N:37]([CH2:38][CH2:39][OH:40])[CH3:36])=[O:29])[N:19]=[CH:18][N:17]=3)=[CH:12][CH:13]=2)[CH:8]=[N:7]1Participants
Procedure
Using the same procedure as in Example 26, methyl (2R)-2-[(4-{[1-(3-fluorobenzyl)-1H-indazol-5-yl]amino}quinazolin-5-yl)oxy]propanoate (205 mg, 0.43 mmol) was reacted with 2-methylaminoethanol (326 mg, 4.3 mmol) to give the title compound as a white solid (124 mg, 56%) except that the reaction mixture was heated at 45° C. for 24 hours and the crude material was purified on an HPLC column (C18, 5 microns, 19 mm diameter, 100 mm length) of a preparative HPLC-MS system eluting with a mixture of water and acetonitrile containing 2 g/l of ammonium carbonate (gradient). NMR Spectrum (2 rotamers) 1.59-1.62 (m, 3H), 3.18 and 2.93 (s, 3H), 3.53-3.65 (m, 4H), 5.00 and 4.74 (t, 1H), 5.71 (s, 2H), 5.90 and 5.81 (q, 1H), 7.05-7.07 (m, 3H), 7.30-7.37 (m, 3H), 7.71-7.77 (m, 2H), 7.82-7.88 (m, 1H), 8.17 (s, 1H), 8.51 (s, 1H), 8.55 and 8.58 (s, 1H), 11.10 (br s, 1H); Mass spectrum MH+ 515.
Sources & evidence
- ORD record
- ord-eae94ef74ad6483b99f8b1aa8d3f61b2
- Source dataset
- uspto-grants-2010_10
- Patent number
- US07820683B2
Reaction notes
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