Trifluoroacetic acid → Diethyl [4-({4-[(2-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-4-yl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)-3-methoxybenzyl]phosphonate trifluoroacetate
Reaction equation
Cl[C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=[C:4]([NH:12][C:13]2[CH:27]=[CH:26][C:16]([CH2:17][P:18](=[O:25])([O:22][CH2:23][CH3:24])[O:19][CH2:20][CH3:21])=[CH:15][C:14]=2[O:28][CH3:29])[N:3]=1.[NH2:30][C:31]1[CH:32]=[CH:33][CH:34]=[C:35]2[C:39]=1[C:38](=[O:40])[N:37]([OH:41])[CH2:36]2.[C:42]([OH:48])([C:44]([F:47])([F:46])[F:45])=[O:43]>>[F:45][C:44]([F:47])([F:46])[C:42]([OH:48])=[O:43].[OH:41][N:37]1[C:38](=[O:40])[C:39]2[C:35](=[CH:34][CH:33]=[CH:32][C:31]=2[NH:30][C:2]2[C:7]([C:8]([F:10])([F:9])[F:11])=[CH:6][N:5]=[C:4]([NH:12][C:13]3[CH:27]=[CH:26][C:16]([CH2:17][P:18](=[O:25])([O:19][CH2:20][CH3:21])[O:22][CH2:23][CH3:24])=[CH:15][C:14]=3[O:28][CH3:29])[N:3]=2)[CH2:36]1Participants
Reactant 3
Product 1
Procedure
The title product was prepared according to the procedure for Example 102 using diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (50.0 mg, 0.11 mmol) and 7-amino-2-hydroxy-2,3-dihydro-1H-isoindol-1-one (Compound 186A, 21.70 mg, 0.13 mmol). The reaction mixture purified by MDP to isolate the desired product (4.6 mg, yield: 7%) as a TFA salt. 1H NMR (CD3OD, 400 MHz): δ=1.29 (t, J=7.2 Hz, 6 H), 3.33 (d, J=21.2 Hz, 2 H), 3.89 (s, 3 H), 4.06-4.13 (m, 4 H), 4.63 (s, 2 H), 4.96 (dt, J=2.8, 8.4 Hz, 1 H), 7.10 (t, J=2.0 Hz, 1 H), 7.24 (d, J=7.6 Hz, 1 H), 7.36 (dd, J=0.8, 8.0 Hz, 0.5 H), 7.52 (m, 1 H), 7.66 (d, J=8.0 Hz, 1 H), 8.32 (d, J=8.0 Hz, 0.5 H), 8.37 (s, 1 H). MS (ES+): m/z 582.17 [MH+]. HPLC: tR=3.64 min (OpenLynx, polar—5 min).
Workup
- customThe title product was prepared
- customThe reaction mixture purified by MDP
Sources & evidence
- ORD record
- ord-8344edde3c5641f78bce335738bccc9a
- Source dataset
- uspto-grants-2015_08
- Patent number
- US09096624B2
Reaction notes
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